Gene Expression Profiling
Sets of structured vocabularies used for describing and categorizing genes, and gene products by their molecular function, involvement in biological processes, and cellular location. These vocabularies and their associations to genes and gene products (Gene Ontology annotations) are generated and curated by the Gene Ontology Consortium.
Carcinoma, Non-Small-Cell Lung
A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289)
Carcinoma, Squamous Cell
A colorless and flammable gas at room temperature and pressure. Ethylene oxide is a bactericidal, fungicidal, and sporicidal disinfectant. It is effective against most micro-organisms, including viruses. It is used as a fumigant for foodstuffs and textiles and as an agent for the gaseous sterilization of heat-labile pharmaceutical and surgical materials. (From Reynolds, Martindale The Extra Pharmacopoeia, 30th ed, p794)
A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.
DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.
Hypoxia-Inducible Factor 1, alpha Subunit
A genus of the family RETROVIRIDAE consisting of non-oncogenic retroviruses that produce multi-organ diseases characterized by long incubation periods and persistent infection. Lentiviruses are unique in that they contain open reading frames (ORFs) between the pol and env genes and in the 3' env region. Five serogroups are recognized, reflecting the mammalian hosts with which they are associated. HIV-1 is the type species.
Brain-Derived Neurotrophic Factor
Carcinoma, Renal Cell
An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and PELLAGRA. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
A multifunctional protein that is found primarily within membrane-bound organelles. In the ENDOPLASMIC RETICULUM it binds to specific N-linked oligosaccharides found on newly-synthesized proteins and functions as a MOLECULAR CHAPERONE that may play a role in PROTEIN FOLDING or retention and degradation of misfolded proteins. In addition calreticulin is a major storage form for CALCIUM and functions as a calcium-signaling molecule that can regulate intracellular calcium HOMEOSTASIS.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Matrix attachment regulates Fas-induced apoptosis in endothelial cells: a role for c-flip and implications for anoikis. (1/360)Survival of endothelial cells is critical for cellular processes such as angiogenesis. Cell attachment to extracellular matrix inhibits apoptosis in endothelial cells both in vitro and in vivo, but the molecular mechanisms underlying matrix-induced survival signals or detachment-induced apoptotic signals are unknown. We demonstrate here that matrix attachment is an efficient regulator of Fas-mediated apoptosis in endothelial cells. Thus, matrix attachment protects cells from Fas-induced apoptosis, whereas matrix detachment results in susceptibility to Fas-mediated cell death. Matrix attachment modulates Fas-mediated apoptosis at two different levels: by regulating the expression level of Fas, and by regulating the expression level of c-Flip, an endogenous antagonist of caspase-8. The extracellular signal-regulated kinase (Erk) cascade functions as a survival pathway in adherent cells by regulating c-Flip expression. We further show that detachment-induced cell death, or anoikis, itself results from activation of the Fas pathway by its ligand, Fas-L. Fas-L/Fas interaction, Fas-FADD complex formation, and caspase-8 activation precede the bulk of anoikis in endothelial cells, and inhibition of any of these events blocks anoikis. These studies identify matrix attachment as a survival factor against death receptor-mediated apoptosis and provide a molecular mechanism for anoikis and previously observed Fas resistance in endothelial cells. (+info)
Global effects of anchorage on gene expression during mammary carcinoma cell growth reveal role of tumor necrosis factor-related apoptosis-inducing ligand in anoikis. (2/360)Anchorage-independent growth is a hallmark of tumor cells. We compared gene expression profiles of anchored and nonanchored human mammary carcinoma cells to study this phenomenon. In this study, we show that anchorage had striking effects on cell growth and morphology but altered transcript levels from a limited number of genes. Only about 1% of mRNA transcripts detected in these cells was altered by anchorage. These include genes related to amino acid and polyamine metabolism, apoptosis, ion channels, cytoskeletal and stress proteins, transcription factors, and growth factors. Some of these may be crucial for the survival of transformed cells. For example, clusterin and the tumor necrosis factor-related apoptosis inducing ligand (TRAIL) were suppressed by anchorage, which could help prevent programmed cell death of these tumor cells. In addition to suppressing TRAIL expression, anchorage also decreased the susceptibility of these tumor cells to TRAIL-induced apoptosis as determined by poly(ADP-ribose) phosphorylase cleavage, annexin-V binding (P < 0.01), and cell cycle analysis (P < 0.0001). These data may help explain mechanisms by which anchorage prevents apoptosis of cells that would otherwise experience anoikis. Thus, genes found to be altered by this analysis could serve as potential targets for anticancer therapy. These findings suggest that TRAIL may be used as a means to target circulating epithelial tumor cells before their attachment and colonization at new sites. (+info)
Anoikis and metastatic potential of cloudman S91 melanoma cells. (3/360)Anoikis is a form of apoptosis induced in normal cells as a result of loss of their adhesion to substrate. In the present study, we have tested whether tumor cells are also sensitive to anoikis and whether selection of tumor cells for resistance to anoikis could increase their metastatic ability. In vitro cultured Cloudman S91 melanoma cells are strongly adherent to the plastic. Prevention of their adherence by rocking or by covering culture plates with polyhydroxyethylmethacrylate resulted in induction of anoikis and death of almost all cells. Their death was prevented in the presence of caspase inhibitor Z-Val-Ala-Asp-fluoromethyl ketone. To select anoikis-resistant cells, S91 cells floating in the culture medium were sequentially isolated and transferred for seven generations. As a result, a new subline of S91 cells capable of growing in free cell suspension was selected. These S91 nonadherent (S91Nadh) cells were completely resistant to anoikis and manifested higher metastatic ability than S91Adh cells. Anoikis resistance of S91Nadh cells was not attributable to their resistance to other apoptotic signals in vitro, and they showed no increase in their survival in vivo in the lungs after i.v. inoculation. Increased metastatic potential of the anoikis-resistant S91Nadh cells was associated with various phenotypic changes, including increased proliferation and loss of VLA-4 integrin expression because of down-regulation of the VLA-49alpha (CLD49d) gene. In parallel, they showed a reduction in homotypic aggregation and binding to endothelial cells, increased Matrigel invasiveness, and decreased matrix metalloproteinase-2 and matrix metalloproteinase-9 activity that paralleled up-regulation of the TIMP-1 gene. S91Nadh cells also manifested changes in cell surface carbohydrates, such as appearance of alpha-galactosyl epitopes as a result of up-regulation of the alpha1,3-galactosyltransferase gene and concomitant reduction in cell membrane sialylation. Thus, selection of S91 melanoma cells for anoikis resistance resulted in an increase in their metastatic potential in parallel with multiple alterations in their phenotypic properties. (+info)
Tyrosine kinase-dependent, phosphatidylinositol 3'-kinase, and mitogen-activated protein kinase-independent signaling pathways prevent lung adenocarcinoma cells from anoikis. (4/360)Normal epithelial cells are anchorage-dependent. Detachment of normal epithelial cells from their substratum causes apoptosis, termed anoikis. Malignant tumor cells, however, can survive and proliferate independent of anchorage. To understand the molecular basis of tumor cell anchorage independence, we investigated the role of tyrosine kinases and their downstream signaling pathways in anoikis resistance of human lung adenocarcinoma cells. Four of the five lung adenocarcinoma cell lines analyzed are resistant to anoikis. Tyrosine kinase inhibitor genistein rendered three of them sensitive to anoikis. Although cell detachment induced rapid protein tyrosine dephosphorylation in Madin-Darby canine kidney cells, a nontransformed epithelial cell line, tyrosine phosphorylation of several proteins in the tumor cells is anchorage-independent. Similarly, phosphorylation of Akt and mitogen-activated protein kinase, two signaling proteins downstream of tyrosine kinases, was decreased in Madin-Darby canine kidney cells but increased in some of the tumor cells upon cell detachment. Inhibition of phosphorylation of the two proteins, however, did not induce anoikis in the tumor cells. Specific inhibitors to several known tyrosine kinases also failed to induce anoikis in these cells. These data suggest the existence of tyrosine kinase-dependent phosphatidylinositol 3'-kinase and mitogen-activated protein kinase-independent signaling pathways that function to regulate cell survival and death. Alteration in these pathways may count for the anchorage-independent survival of the lung adenocarcinoma cells and other malignant tumor cells. (+info)
Caspases as key executors of methyl selenium-induced apoptosis (anoikis) of DU-145 prostate cancer cells. (5/360)Apoptosis induction may be a mechanism mediating the anticancer activity of selenium. Our earlier work indicated that distinct cell death pathways are likely involved in apoptosis induced by the CH3SeH and the hydrogen selenide pools of selenium metabolites. To explore the role of caspases in cancer cell apoptosis induced by selenium, we examined the involvement of these molecules in the death of the DU-145 human prostate carcinoma cells induced by methylseleninic acid (MSeA), a novel penultimate precursor of the putative critical anticancer metabolite CH3SeH. Sodium selenite, a representative of the genotoxic selenium pool, was used as a reference for comparison. The results show that MSeA-induced apoptosis was accompanied by the activation of multiple caspases (caspase-3, -7, -8, and -9), mitochondrial release of cytochrome c (CC), poly(ADP-ribose) polymerase (PARP) cleavage, and DNA fragmentation. In contrast, selenite-induced apoptotic DNA fragmentation was observed in the absence of these changes, but was associated with the phosphorylation of c-Jun-NH2-terminal kinase 1/2 and p38 mitogen-activated protein kinase/stress-activated protein kinase 2. A general caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-(OMe) fluoromethyl ketone, blocked MSeA-induced cleavage of procaspases and PARP, CC release, and DNA nucleosomal fragmentation, but did not prevent cell detachment. Furthermore, PARP cleavage and caspase activation were confined exclusively to detached cells, indicating that MSeA induction of cell detachment was a prerequisite for caspase activation and apoptosis execution. This process therefore resembled "anoikis," a special mode of apoptosis induction in which adherent cells lose contact with the extracellular matrix. Additional experiments with irreversible caspase inhibitors show that MSeA-induced anoikis involved caspase-3- and -7-mediated PARP cleavage that was initiated by caspase-8 and probably amplified through CC-caspase-9 activation and a feedback activation loop from caspase-3. Taken together, the data support a methyl selenium-specific induction of DU-145 cell apoptosis that involves cell detachment as a prerequisite (anoikis) and is executed principally through caspase-8 activation and its cross-talk with multiple caspases. (+info)
Apoptotic signaling during initiation of detachment-induced apoptosis ("anoikis") of primary human intestinal epithelial cells. (6/360)Apoptosis after the loss of cell anchorage--"anoikis"--plays an important role in the life cycle of adherent cells. Furthermore, loss of anchorage dependency is believed to be a critical step in metastatic transformation. The aim of this study was to further characterize the sequence of intracellular events during anoikis in a nontransformed population of human intestinal epithelial cells (IECs). Purified human IECs were kept in suspension to induce anoikis in over 90% of IECs within 3 h. Two initiator caspases, caspase-2 and -9, are activated within 15 min, followed by the hierarchical activation of downstream caspases within 1 h. The activation of the caspase FLICE (caspase-8) does not contribute to the initiation of anoikis, and massive release of cytochrome c from mitochondria cannot be detected before 60 min, indicating that cytochrome c release does not play a role during initiation of anoikis. This study delineates the signaling cascade during anoikis of nontransformed cells. Future studies may identify alterations of this cascade in neoplastic cells, thereby possibly gaining insight into carcinogenesis and metastatic transformation. (+info)
Smad7 inhibits the survival nuclear factor kappaB and potentiates apoptosis in epithelial cells. (7/360)In this study, we examined the effect of the stable expression of Smad7 in two different cell lines on apoptosis induced by various stimuli including TGF-beta, serum withdrawal, loss of cell adhesion (anoikis) and TNF-alpha. Smad7 increased TGF-beta-mediated apoptosis in Mv1Lu cells as well as anoikis and/or serum withdrawal-induced apoptosis in Mv1Lu and MDCK cells. Smad7 markedly decreased the activity of the survival NF-kappaB transcription factor in MDCK cells. Interestingly, the stable expression of oncogenic Ras in MDCK cells which suppressed Smad7 inhibition of NF-kappaB also suppressed Smad7 potentiation of serum withdrawal-induced apoptosis and anoikis. In addition, Smad7 inhibited TNF-alpha stimulation of NF-kappaB and increased TNF-alpha-mediated apoptosis in MDCK cells. Our results provide the first evidence that Smad7 induces sensitization of cells to different forms of cell death. They moreover demonstrate that Smad7 inhibits the survival NF-kappaB factor, providing a potential mechanism whereby Smad7 potentiates cell death. (+info)
Human intestinal epithelial cell survival: differentiation state-specific control mechanisms. (8/360)To investigate whether human intestinal epithelial cell survival involves distinct control mechanisms depending on the state of differentiation, we analyzed the in vitro effects of insulin, pharmacological inhibitors of Fak, MEK/Erk, and PI3-K/Akt, and integrin (beta1, beta4)-blocking antibodies on the survival of the well-established human Caco-2 enterocyte-like and HIEC-6 cryptlike cell models. In addition, relative expression levels of six Bcl-2 homologs (Bcl-2, Bcl-X(L), Mcl-1, Bax, Bak, and Bad) and activation levels of Fak, Erk-2, and Akt were analyzed. Herein, we report that 1) the enterocytic differentiation process results in the establishment of distinct profiles of Bcl-2 homolog expression levels, as well as p125(Fak), p42(Erk-2), and p57(Akt) activated levels; 2) the inhibition of Fak, of the MEK/Erk pathway, or of PI3-K, have distinct impacts on enterocytic cell survival in undifferentiated (subconfluent Caco-2, confluent HIEC-6) and differentiated (30 days postconfluent Caco-2) cells; 3) exposure to insulin and the inhibition of Fak, MEK, and PI3-K resulted in differentiation state-distinct modulations in the expression of each Bcl-2 homolog analyzed; and 4) Fak, beta1 and beta4 integrins, as well as the MEK/Erk and PI3-K/Akt pathways, are distinctively involved in cell survival depending on the state of cell differentiation. Taken together, these data indicate that human intestinal epithelial cell survival is regulated according to differentiation state-specific control mechanisms. (+info)
Tyrosine receptor kinase B silencing inhibits anoikis‑resistance and improves anticancer efficiency of sorafenib in human renal...
Establishment of anoikis-resistant cell model in vitro is usually on the basis of suspension culture that prevents cells from attachment (23-25). Therefore, we chose ultra-low attachment plates for the continuous suspension culture of the parental ACHN cells for 10 days, and the re-adherent cells were regarded as anoikis-resistant ACHN cells. Our data revealed that anoikis-resistant ACHN cells were characterized with more aggressive malignant biological behavior, including more rapid proliferation, less detachment-induced apoptosis and more capable of invasion in contrast to parental cells.. The molecular mechanisms involved in anoikis-resistance have been extensively investigated. PI3Ks are a family of lipid kinases that phosphorylate the 3′-OH group on phosphatidylinositols in the plasma membrane, resulting in recruitment of Akt to cell membrane for activation, which regulates tumor growth and survival (26). Likewise, MEK/ERK is the most typical mitogen activated protein kinase (MAPK) ...
PLK1 Is Transcriptionally Activated by NF-κB during Cell Detachment and Enhances Anoikis Resistance through Inhibiting β...
Recent studies have indicated that detachment of epithelial cells triggers not only pro-apoptotic but also anti-apoptotic signals, and the equilibrium between these signals regulates anoikis (22-24). In suspended carcinoma cells, survival signals typically prevail, and anoikis induction is blocked, ultimately leading to tumor invasion and metastasis. Several anti-anoikis signals in cancer cells have been identified. For example, we and other researchers found that the activation of oncoproteins, including CTTN (14), calreticulin (15), Ras (25, 26), and β-catenin (17), suppressed anoikis of various types of cancer cells. In the present study, we found that detachment of ESCC cells triggered the upregulation of PLK1, a critical anti-apoptotic protein. Overexpression of PLK1 blocked anoikis in detached cells, and inhibition or depletion of PLK1 restored the sensitivity of ESCC cells to anoikis. Furthermore, it was noticed that PLK1 depletion did not affect the expression level of CTTN and ...
Figure 4 | Prolonged Nitric Oxide Exposure Enhances Anoikis Resistance and Migration through Epithelial-Mesenchymal Transition...
Figure 4: Prolonged Nitric Oxide Exposure Enhances Anoikis Resistance and Migration through Epithelial-Mesenchymal Transition and Caveolin-1 Upregulation
Suppression of anoikis in human intestinal epithelial cells: differentiation state-selective roles of α2β1, α3β1, α5β1, and...
Regulation of anoikis in human intestinal epithelial cells (IECs) implicates differentiation state-specific mechanisms. Human IECs express distinct repertoires of integrins according to their state of differentiation. Therefore, we investigated whether α2β1, α3β1, α5β1, and α6β4 integrins perform differentiation state-specific roles in the suppression of IEC anoikis. Human (HIEC, Caco-2/15) IECs were exposed to specific antibodies that block the binding activity of integrin subunits (α2, α3, α5, α6, β1 or β4) to verify whether or not their inhibition induced anoikis. The knockdown of α6 was also performed by shRNA. Additionally, apoptosis/anoikis was induced by pharmacological inhibition of Fak (PF573228) or Src (PP2). Anoikis/apoptosis was assayed by DNA laddering, ISEL, and/or caspase activity (CASP-8, -9, or -3). Activation levels of Fak and Src, as well as functional Fak-Src interactions, were also assessed. We report herein that differentiated IECs exhibit a greater sensitivity to
TGF-beta has paradoxical and context dependent effects on proliferation and anoikis in human colorectal cancer cell lines. -...
Transforming growth factor-beta (TGF-beta) is a pluripotent cytokine that can have both tumor suppressing and tumor promoting effects on epithelial cells. It is unclear what determines when TGF-beta and its signaling pathway act predominantly as a tumor suppressor pathway or as a tumor-promoter pathway and whether TGF-beta can have both classes of effects concurrently on a cell. We investigated the effect of TGF-beta on anoikis in colorectal cancer cell lines sensitive to TGF-beta-mediated growth inhibition to determine if the context of the cells could be one of the factors that would affect whether TGF-beta exerts tumor suppressor or oncogene activity on colon cancer cells. We observed variable effects of TGF-beta on anoikis in these cell lines, even though they all are growth-inhibited by TGF-beta. Thus, we show that TGF-beta has variable effects on anoikis in colon cancer cell lines that likely reflects the effects of concurrent gene mutations in the cancer cells and the activation state of ...
HAb18G/CD147 cell-cell contacts confer resistance of a HEK293 subpopulation to anoikis in an E-cadherin-dependent manner | BMC...
Anoikis resistance is a key to the survival of cells in malignant transformation and metastasis [18, 19]. It may also be a key to the adaptation of cells to suspension culture and spheroids growth used in engineering. For epithelial cells, suppression of anoikis upon detachment seems to be induced when cell-cell contacts are formed. For example, cadherin-mediated homotypic interactions maintain the survival of human prostate carcinoma DU-145 cells in the absence of extracellular matrix (ECM) attachments . Also, disruption of E-cadherin cell-cell contacts showed more important for suppressing anoikis of normal enterocytes after detachment from villus epithelium, as compared to cell-ECM disruption . Growth as spheroids renders tumor cells less sensitive to exogenous apoptotic stimuli, and spheroids have greater drug resistance than the corresponding monolayers ; and some cells used in engineering also grow as spheroids in suspension. Thus, elucidating the mechanisms by which spheroids ...
Preclinical and early clinical trials indicate that up to 50% of triple-negative breast cancers (TNBC) express androgen receptor (AR) and are potentially responsive to anti-androgens. However, the function of AR in TNBC and the mechanisms by which AR-targeted therapy reduces tumor burden are largely unknown. We hypothesized that AR maintains a cancer stem cell (CSC)-like tumor initiating population and serves as an anti-apoptotic factor, facilitating anchorage independence and metastasis. AR levels increased in TNBC cells grown in forced suspension culture compared to those in attached conditions, and cells that expressed AR resisted detachment-induced apoptosis. Culturing TNBC cells in suspension increased the CSC-like population, an effect reversed by AR inhibition. Pre-treatment with enzalutamide (Enza) decreased the tumor-initiating capacity of TNBC cells and reduced tumor volume and viability when administered simultaneously or subsequent to the chemotherapeutic paclitaxel; simultaneous ...
Hypoxia-Inducible Factor 1α Mediates Anoikis Resistance via Suppression of α5 Integrin | Cancer Research
Cell culture and chemicals. The human gastric cancer cell lines AGS (CRL-1739; American Type Culture Collection) and MKN28 (JCRB Cell Bank) were grown in monolayer cultures in recommended medium. 2-Methoxyestradiol (2ME2) and diphenyleneiodonium (DPI) chloride were purchased from Sigma-Aldrich and dissolved in DMSO at a concentration of 30 and 10 mmol/L, respectively.. Plasmid construction and production of lentiviral vectors. Short hairpin RNA (shRNA) sequences against human HIF-1α and scrambled control oligonucleotides (TIB MOLBIOL) were published elsewhere ( 3, 4). Oligonucleotides were inserted into BsrGI and XbaI restriction sites of the lentiviral bicistronic vector pPR1, which allows for coexpression of GFP ( 5). Lentiviruses were produced by transient transfection of pPR-HIF-1α or pPR-scr with packaging vectors in 293T cells using the calcium-phosphate method. Vector titers were determined by transducing 293T cells with serial dilutions of concentrated lentivirus, and green fluorescent ...
anoikis - oi
A form of programmed cell death (apoptosis) induced in certain cell types when they become detached from their extracellular matrix or from a surface. Epithelial, endothelial, and many other tissue cells depend on continual interchange of signals with neighbouring cells and their immediate environment in order to survive. The absence of such signals following detachment from the matrix normally results in death of the cell. However, when tumour cells detach they resist anoikis, allowing them to migrate to new sites and seed new tumours. The reasons for this are unknown: one theory is that overexpression of the NTRK1 receptor for nerve growth factor (see neurotrophin) somehow enables cells to escape anoikis. The term is derived from the Greek word for homelessness. ...
Tension testing in adherent cells | JCB
Like soloing rock climbers, adherent cells need a good handhold to survive. Ma et al. now identify an adaptor protein that monitors the cells grip and signals death if the grip fails.. Death following detachment, known as anoikis, is a form of programmed cell death that ensures the disposal of displaced adherent cells. Lack of anoikis is thought to give cells metastatic potential.. A number of survival factors have been identified that are activated by integrin attachment to the extracellular matrix. Binding to soluble matrix fragments, rather than to a fixed matrix, does not prevent anoikis. This difference suggests that mechanical tension is also being measured.. Inside the cell, integrins associate with signaling adaptor proteins of the Shc family. One family member, p66Shc, has been suggested to promote apoptosis. The team now shows that an epithelial cell line that resists anoikis does not express p66Shc. Giving these cells back some p66Shc reestablished detachment-induced death. Normal ...
Context-specific protein tyrosine kinase 6 (PTK6) signalling in prostate cancer - Zheng - 2013 - European Journal of Clinical...
We identified AKT, p130CAS and focal adhesion kinase (FAK) as novel PTK6 substrates and demonstrated their roles in promoting cell proliferation, migration and resistance to anoikis. In prostate cancer cells, active PTK6 is primarily associated with membrane compartments, although the majority of total PTK6 is localized within the cytoplasm. Ectopic expression of membrane-targeted PTK6 transforms immortalized fibroblasts. Knockdown of endogenous cytoplasmic PTK6 in PC3 prostate cancer cells impairs proliferation, migration and anoikis resistance. However, re-introduction of PTK6 into the nucleus significantly decreases cell proliferation, suggesting context-specific functions for nuclear PTK6. ...
negative regulation of anoikis Antibodies | Invitrogen ...
Antibodies for proteins involved in negative regulation of anoikis pathways, according to their Panther/Gene Ontology Classification
Il Destino delle cellule muscolari lisce vasali è controllato dal genere - UnissResearch
Gender differences are detectable in cardiovascular diseases and reactive oxygen species (ROS) play a pivotal role in the pathogenesis of vascular disease. In this study we aimed to investigate redox state and cell fate in vascular smooth muscle cells (VSMC), which play a role in several cardiovascular diseases, such as hypertension and atherosclerosis, isolated from male and female rat (MVSMC and FVSMC), in basal condition and after induction of oxidative stress by UVB radiation. We found that FVSMC have a more favourable redox balance in comparison with MVSMC both in basal conditions and after UVB irradiation. Accordingly, MVSMC are more susceptible to radiation-induced stress and easier underwent apoptosis in comparison to FVSMC which clearly displayed signs of premature senescence and anoikis resistance that can be due to their cytoskeleton-dependent adhesion features and to a higher propensity to undergo autophagy and survival in unfavourable environmental conditions. Moreover, in FVSMC, ...
Bcl2l11 - Bcl-2-like protein 11 - Mus musculus (Mouse) - Bcl2l11 gene & protein
Induces apoptosis and anoikis. The isoforms vary in cytotoxicity with isoform BimS being the most potent and isoform BimEL being the least potent.
THREE TOPICS IN PARALLEL COMMUNICATIONS - TechyLib
το κείμενο με τίτλο THREE TOPICS IN PARALLEL COMMUNICATIONS σχετίζετε με Λογισμικό & κατασκευή λογ/κού
Aberrant expression of cortactin in head and neck squamous cell carcinoma cells is associated with enhanced cell proliferation...
The CTTN gene (formerly designated EMS1), encodes cortactin, a key regulator of dynamic actin networks. Both CTTN and CCND1, the latter encoding the cell cycle regulator cyclin D1, reside at chromosomal locus 11q13, a region commonly amplified in breast cancers and head and neck squamous cell carcinoma (HNSCC). Previously, we identified a novel role for cortactin in cancer cells, whereby cortactin overexpression attenuated ligand-induced down-regulation of the epidermal growth factor (EGF) receptor (EGFR), leading to sustained signaling. However, how this affected growth factor-induced cellular responses was unclear. Here, by modulation of cortactin expression in a panel of HNSCC cell lines, we show that cortactin overexpression enhances serum- and EGF-stimulated proliferation under both anchorage-dependent and anchorage-independent conditions and also increases resistance to anoikis (detachment-induced apoptosis). These effects are associated with increased activation of extracellular signal-regulated
NIOSHTIC-2 Publications Search - 20043481 - Monosaccharide digitoxin derivative sensitize human non-small cell lung cancer...
Advanced stage cancers acquire anoikis resistance which provides metastatic potential to invade and form tumors at distant sites. Suppression of anoikis resistance by novel molecular therapies would greatly benefit treatment strategies for metastatic cancers. Recently, digitoxin and several of its novel synthetic derivatives, such as -L-rhamnose monosaccharide derivative (D6-MA), have been synthe
Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways. | Broad Institute
Loss of the epithelial adhesion molecule E-cadherin is thought to enable metastasis by disrupting intercellular contacts-an early step in metastatic dissemination. To further investigate the molecular basis of this notion, we use two methods to inhibit E-cadherin function that distinguish between E-cadherins cell-cell adhesion and intracellular signaling functions. Whereas the disruption of cell-cell contacts alone does not enable metastasis, the loss of E-cadherin protein does, through induction of an epithelial-to-mesenchymal transition, invasiveness, and anoikis resistance. We find the E-cadherin binding partner beta-catenin to be necessary, but not sufficient, for induction of these phenotypes. In addition, gene expression analysis shows that E-cadherin loss results in the induction of multiple transcription factors, at least one of which, Twist, is necessary for E-cadherin loss-induced metastasis. These findings indicate that E-cadherin loss in tumors contributes to metastatic ...
A ZEB1-HDAC pathway enters the epithelial to mesenchymal transition world in pancreatic cancer | Gut
Epithelial to mesenchymal transition (EMT) correlates with high-grade malignancy including the competence to form metastases. In addition, EMT has recently been linked to cellular self-renewal programmes of cancer stem cells and apoptosis/anoikis resistance, which are all features of therapeutic resistance. The EMT programme is driven by several transcription factors (TFs), such as the transcriptional regulators SNAIL, SLUG, ZEB1 and ZEB2 and the basic helix-loop-helix factors E47 and TWIST. These proteins target and repress the CDH1 gene, which encodes for E-cadherin, an important caretaker of the epithelial state. Expression studies in human pancreatic cancer showed expression of SNAIL in 78% and of SLUG in 50% of cases.1 Although no or low levels of TWIST are expressed in pancreatic cancers, up-regulation of this gene under hypoxic condition may argue for a contribution towards tumour progression.1 2 Expression of the ZEB2 gene was recently found to be silenced by promoter methylation in the ...
Septin and Ras regulate cytokinetic abscission in detached cells | Cell Division | Full Text
Integrin-mediated adhesion is normally required for cytokinetic abscission, and failure in the process can generate potentially oncogenic tetraploid cells. Here, detachment-induced formation of oncogenic tetraploid cells was analyzed in non-transformed human BJ fibroblasts and BJ expressing SV40LT (BJ-LT) ± overactive HRas. In contrast to BJ and BJ-LT cells, non-adherent BJ-LT-Ras cells recruited ALIX and CHMP4B to the midbody and divided. In detached BJ and BJ-LT cells regression of the cytokinetic furrow was suppressed by intercellular bridge-associated septin; after re-adhesion these cells divided by cytofission, however, some cells became bi-nucleated because of septin reorganization and furrow regression. Adherent bi-nucleated BJ cells became senescent in G1 with p21 accumulation in the nucleus, apparently due to p53 activation since adherent bi-nucleated BJ-LT cells passed through next cell cycle and divided into mono-nucleated tetraploids; the two centrosomes present in bi-nucleated BJ cells
Focal Adhesion Kinase | Emerging Understanding of Bcl-2 Biology
Data Availability StatementNot applicable Abstract Background While aberrant activation from the chromatin-remodeling SWI/SNF complexes continues to be connected with cancers development and advancement, the role of every subunit in tumor cells is described poorly. cancer tumor cells and sensitized tumor cells to anoikis. In response to lack of connection, SMARCE1 interacted with and potentiated transcriptional activity of HIF1A, leading to speedy PTK2 activation. Both HIF1A and PTK2 were indispensable for SMARCE1-mediated safety against anoikis by advertising activation of ERK and AKT pathways while suppressing the manifestation of pro-apoptotic BIM protein. Expression data analysis of a large cohort of human being breast tumors exposed that high manifestation of SMARCE1 or PTK2 is definitely associated with poor prognosis and tumor relapse, and PTK2 manifestation is definitely positively correlated with SMARCE1 manifestation in basal-like and luminal B subtypes of breast tumors. Conclusions ...
Effects of TCS on anchorage-independent growth of anoik | Open-i
Effects of TCS on anchorage-independent growth of anoikis resistant H460 cells.(A) Cells were pretreated with TCS (0-7.5 µM) for 24 h and subjected to soft a
Foretinib (GSK1363089), an Orally Available Multikinase Inhibitor of c-Met and VEGFR-2, Blocks Proliferation, Induces Anoikis,...
This study reports on the efficacy and mechanism of action of the small-molecule multikinase inhibitor foretinib in preclinical models of ovarian cancer metastasis. Our data suggest 4 principal mechanisms for how foretinib inhibits ovarian cancer growth and metastasis. In ovarian cancer cell lines, the inhibitor: (i) blocked activation of c-Met signaling; (ii) reduced proliferation mediated by a G2-M cell-cycle arrest; (iii) induced cell death through a 2-step mechanism in which cells detach followed by a caspase-dependent form of anoikis; and (iv) reduced proliferation, adhesion, migration, and invasion during early tumor development. In mouse models of ovarian cancer metastasis, foretinib reduced tumor burden and metastasis mediated by reduced angiogenesis, proliferation, and increased apoptosis. The multiple activities of foretinib are consistent with the numerous effects that have been attributed to c-Met and angiogenesis in the context of cancer (3).. Foretinib targets c-Met and VEGFR-2 ...
Antitumor activity of [Pt(O,O-acac)(γ-acac)(DMS)] in mouse xenograft model of breast cancer<...
TY - JOUR. T1 - Antitumor activity of [Pt(O,O-acac)(γ-acac)(DMS)] in mouse xenograft model of breast cancer. AU - Muscella, A.. AU - Vetrugno, C.. AU - Migoni, D.. AU - Biagioni, F.. AU - Fanizzi, F. P.. AU - Fornai, F.. AU - De Pascali, S. A.. AU - Marsigliante, S.. PY - 2014. Y1 - 2014. N2 - The higher and selective cytotoxicity of [Pt(O,O-acac)(γ-acac)(DMS)] toward cancer cell in both immortalized cell lines and in breast cancer cells in primary cultures, stimulated a pre-clinical study so as to evaluate its therapeutic potential in vivo. The efficacy of [Pt(O,O-acac)(γ-acac)(DMS) ] was assessed using a xenograft model of breast cancer developed by injection of MCF-7 cells in the flank of BALB/c nude mice. Treatment of solid tumor-bearing mice with [Pt(O,O-acac)(γ-acac)(DMS)] induced up to 50% reduction of tumor mass compared with an average 10% inhibition recorded in cisplatin-treated animals. Thus, chemotherapy with [Pt(O,O-acac)(γ-acac) (DMS)] was much more effective than ...
Epithelial ovarian cancer is the most lethal gynecological malignancy and the fifth leading cause of cancer death in women in the Western world. ETS transcription factors have been implicated in the regulation of gene expression during a variety of biological processes including cell growth and differentiation. We recently examined the role of the ETS transcription factor ETV5 in epithelial ovarian cancer and described ETV5 as being up-regulated in ovarian tumor samples as compared to ovarian tissue controls. In ovarian cancer cells, we showed that ETV5 regulated the expression of cell adhesion molecules, enhancing ovarian cancer cell survival in anchorage-independent conditions and suggesting that it plays a role in ovarian cancer cell dissemination and metastasis into the peritoneal cavity To understand the role of ETV5 transcription factor during ovarian cancer cell dissemination, we analyzed by gene expression microarray technology those genes whose expression was altered in an ovarian ...
Supplementary Materialsoncotarget-08-44654-s001. prostate cancer. In fact, Gal-8 AS-605240 distributor regulates | Beneficial...
Supplementary Materialsoncotarget-08-44654-s001. prostate cancer. In fact, Gal-8 AS-605240 distributor regulates the rearrangement from the E-Cadherin and cytoskeleton manifestation, with a significant effect on anoikis and homotypic aggregation of tumour cells, both becoming essential functions for the success of circulating tumour cells during metastasis. While localized prostate tumor can be healed, advanced and metastatic disease continues to be a substantial restorative problem, urging for the recognition of prognostic markers from the metastatic procedure. Collectively, our outcomes highlight Galectin-8 like a potential focus on for anti-metastatic therapy against prostate tumor. (magnification, x40). (f) Evaluation of long-term spontaneous metastasis to draining lymph nodes from mice after resection of major subcutaneous tumour. Representative images of metastatic or regular lymph nodes are shown. Scale pub: 2.5 mm. Histological AS-605240 distributor analyses by revised Masson Trichrome ...
International Medical Rights (IMR) Agency
This book focuses on the functional significance of targeting apoptosis for the treatment of prostate cancer. New concepts on the challenges relating to the development of resistance by androgen-independent tumors are introduced, in terms of the contribution of anoikis and cross-talk of androgens with key growth factor signaling pathways. This volume also provides insightful discussion on the exploitation of the apoptotic and angiogenic synergism towards complete eradication of prostate tumors. Last but not least, it includes reflections on the drug development challenge based on the analysis of data from existing clinical trials. ...
Cell detachment upregulates Fas expression in HUVECs. ( | Open-i
Cell detachment upregulates Fas expression in HUVECs. (A) Detachment induces cell surface levels of Fas. HUVECs were kept adherent or in suspension for 12 h. FA
Patente US5004057 - Drill bit with improved steerability - Google Patentes
A drill bit offering improved steerability. Drill bits include gage sections which are adapted to facilitate deflection of the bits within a borehole to facilitate navigational or directional drilling. The gage portions of the bit may be arranged in an arcuate path around a portion of the periphery of the bit. Also, the bit portions may be spaced and adapted to serve, at least in part, as fulcrums, to facilitate deflection of the bit and the bringing of gage cutting portions of the bit in contact with the sidewalls of the borehole.
Text using 6-bit ASCII - IALA AISM
NOTE 1 - When a 6-bit spare is needed to satisfy the 8-bit byte boundary rule, the 6-bit spare will be interpreted as a valid 6-bit character (all zeros is the @ character). This is the case when the number of characters is: 1, 5, 9, 13,17, 21, 25, etc ...
Posted a comment on discussion Open Discussion on Practically Random Well, youve got correct numbers, now. Question: Why are you calling them 63-bit numbers? If they have sign, then they can still be ordered as 64-bit numbers. So, treat them as 64-bit numbers and call it good. For this test it does not actually matter whether you order them as signed or unsigned. Hopefully. They are 63 bit values because they are made by taking the most significant 21 bits from 3 consecutive 32-bit PRNG outputs and concatonating them. 21 times 3 is 63. The 63 bits are stored in 64... ...
New Vegas a bit rewritten and a bit redesigned | No Mutants Allowed
This is 2.0 version of my previous thread. While I enjoyed the previous one, it got a bit messy and crowded. The idea is the same, we fix and change...
中国科学院海洋研究所机构知识库(IOCAS-IR): Marine Bacterial Polysaccharide EPS11 Inhibits Cancer Cell Growth via Blocking Cell Adhesion and...
Tumor cells that acquire metastatic potential have developed resistance to anoikis, a cell death process, after detachment from their primary site to the second organ. In this study, we investigated the molecular mechanisms of a novel marine bacterial polysaccharide EPS11 which exerts its cytotoxic effects through affecting cancer cell adhesion and anoikis. Firstly, we found that EPS11 could significantly affect cell proliferation and block cell adhesion in A549 cells. We further demonstrated that the expression of several cell adhesion associated proteins is downregulated and the filiform structures of cancer cells are destroyed after EPS11 treatment. Interestingly, the destruction of filiform structures in A549 cells by EPS11 is in a dose-dependent manner, and the inhibitory tendency is very consistent with that observed in the cell adhesion assay, which confirms that filiform structures play important roles in modulating cell adhesion. Moreover, we showed that EPS11 induces apoptosis of A549 ...
Multiple post-translational modifications regulate E-cadherin transport during apoptosis | Journal of Cell Science
E-cadherin is synthesized as a precursor and then undergoes cleavage by proprotein convertases. This processing is essential for E-cadherin maturation and cell adhesion. Loss of cell adhesion causes detachment-induced apoptosis- anoikis. Anoikis can be inhibited despite loss of cell-matrix interactions by preserving E-cadherin mediated cell-cell adhesion. Conversely, acute loss of E-cadherin sensitizes cells to apoptosis by unknown post-translational mechanisms. In response to drug treatment of breast cancer cells, our analysis revealed that two independent modifications of E-cadherin inhibit its cell surface transport. Firstly, O-linked beta-N-acetylglucosamine (O-GlcNAc) modification of the cytoplasmic domain retains E-cadherin in the endoplasmic reticulum. Secondly, incomplete processing by proprotein convertases arrests E-cadherin transport late in the secretory pathway. We demonstrated these E-cadherin modifications (detected by specific lectins and antibodies) do not affect binding to ...
Effect of hydroxychloroquine and characterization of autophagy in a mouse model of endometriosis
In endometriosis, the increased survival potential of shed endometrial cells (which normally undergo anoikis) is suggested to promote lesion development. One mechanism that may alter anoikis is autophagy. Using an autophagic flux inhibitor hydroxychloroquine (HCQ), we identified that it reduces the in vitro survival capacity of human endometriotic and endometrial T-HESC cells. We also identified that HCQ could decrease lesion numbers and disrupt lesion histopathology, as well as increase the levels of peritoneal macrophages and the IP-10 (10 kDa interferon-γ-induced protein) chemokine in a mouse model of endometriosis. We noted that RNA levels of a subset of autophagic markers were reduced in lesions relative to uterine horns from endometriosis-induced (untreated) mice. In addition, the RNA levels of autophagic markers were decreased in uterine horns of endometriosis-induced mice compared with those from controls. However, we noted that protein expression of LC3B (microtubule-associated protein ...
The University of Auckland Library Trefoil Factor-1 (TFF1) belongs to the family of trefoil factor peptides. Trefoil factors protect the gastrointestinal tract against mucosal injury. Trefoil peptides are upregulated and secreted in an autocrine and paracrine fashion in response to gastrointestinal injury. They facilitate cell migration and prevent anoikis. TFF1 is also expressed in various tissues and regulated by multiple cellular processes. Several studies have also demonstrated increased expression of TFF1 in a high percentage of mammary and prostate carcinoma cases. However, the functional role of autocrine TFF1 in mammary and prostate carcinoma has not been previously elucidated. Herein, I demonstrate that forced expression of TFF1 in mammary carcinoma cells resulted in increased total cell number as a consequence of increased cell proliferation and survival. Forced expression of TFF1 enhanced anchorage-independent growth and promoted scattered cell morphology with increased cell migration ...
Cancer is a dominant and common disease that claims the lives of many people in the world. Metastasis is a type of cancer that is characterized by malignancy. Metastasis is the combination of the early invasion and late colonization of cancer cells. Learn more about Oncotarget at Research Gate. Typically, cancer cells experience morphological transformation and change their cell-cell matrix connection to pass through the first stage of the multistep process of metastasis. The epithelial-mesenchymal transition (EMT) is a critical stage in the early events of tumor cell metastatic supply by supporting the cells with more invasive, motile potential. On the other side, Mesenchymal-epithelial transition (MET) is needed to move the cells to extravasated from the vessels into their tissue to create micrometastases. The micrometastases will eventually develop a secondary tumor after the cells survive anoikis process. Check Oncotarget journal at scimagojr.com. Long-coding RNAs (LncRNAs) are categories of ...
Intraperitoneal seeding is a distinctive pattern of dissemination that is unique to EOC and markedly differs from the hematogenous or lymphatic metastasis found for many other types of tumors. A key and initial rate-limiting step in the seeding of EOC is the survival of floating tumor cells in the peritoneal fluid. It is widely recognized that aggregation enables floating tumor cells to escape anoikis, although it is unclear whether tumor cells shed into the peritoneal fluid as aggregates or shed as single cells that then assemble into aggregates (3). The mechanisms that mediate adhesion between floating EOC cells are poorly understood. EOC cells express several integrins and extracellular matrix (ECM) proteins, and interactions between α5β1 integrin and fibronectin have been reported to mediate assembly of EOC cells into spheroids (22). Cadherins are transmembrane glycoproteins that have well-established functions in mediating homophilic cell adhesion (7). The role of cadherins in ...
Luconia - La Energia XI
Luconia - La Energia 11 1. Nagel - Amor Philema (Original Mix) 2. Libero - Human Nature (Akira Kayosha Mix) 3. Kamil Polner - Deflector (Original Mix) 4. Anoikis - Morning View 5. Patrick Markus - Square 39 (Original Mix) 6. Nitrous Oxide pres Redmoon - Cumulus (Original Mix) 7. Moxa - Dreamcatcher (Firestorm Mix) 8. Lawrence Palmer - Streamline (Activa vs Tom Colontonio Mix)
Patent US7281189 - Apparatus and method for separately modulating systematic bits and parity ... - Google Patents
A transmission apparatus and method turbo-encode data and output systematic bit and parity bit data. The systematic bit data and the parity bit data are modulated independently of each other such that communication quality is better when a modulation scheme for the systematic bit data is changed than when a modulation scheme for the parity bit data is changed. The systematic bit data and the parity bit data are then transmitted.
Definition of parity bit in US English - a bit which acts as a check on a set of binary values, calculated in such a way that the number of 1s in the set plus th
Little bit of blood in discharge - Things You Didnt Know
Little bit of blood in discharge - Little bit if bright red blood & white creamy discharge, what is this? Period. Could be the beginning of your period or poss. Mis.
Radius router bit
Radius router bit from Metabo - High-quality, reliable and durable. Inform yourself now about the professional power tool range from Metabo.
Bitfields for Digiboard initializing parameters: Bit(s) Description ) 7-5 unused 4-3 parity (00 none, 01 odd, 11 even) 2 stop bits (0 = one, 1 = two) 1-0 data bits (00 = five, 01 = six, 10 = seven, 11 = eight) SeeAlso: #00307,#00308 ...
Before Commenting | CrossWise
All comments are moderated which means I must manually release them before they will appear on the site. Please keep your comments pertinent -- even if a bit tangential -- to the topic of the post. In addition, try to be brief, concise, and respectful. If you have quite a bit to post, it may be best…
and sex is a bit painful (esp upon entry) Sometimes I even bleed a small bit. I am sore for a few days afterwards. Anyone else have this problem?? Just started happening to me. ...
Parasite review by shaynestl •...
This was great! If I had to take any issue with it, Id like to have gotten to know the characters a bit more, but it is already incredibly effective, especially in how it juggles all its tonal shifts.
Extracellular matrix metalloproteinase inducer (CD147) confers resistance of breast cancer cells to anoikis through inhibition...
TY - JOUR. T1 - Extracellular matrix metalloproteinase inducer (CD147) confers resistance of breast cancer cells to anoikis through inhibition of bim. AU - Yang, Jin Ming. AU - ONeill, Peter. AU - Jin, Wei. AU - Foty, Ramsey. AU - Medina, Daniel J.. AU - Xu, Zude. AU - Lomas, Mehnaaz. AU - Arndt, Greg M.. AU - Tang, Yi. AU - Nakada, Marian. AU - Yan, Li. AU - Hait, William N.. PY - 2006/4/7. Y1 - 2006/4/7. N2 - Overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN or CD147), a member of the immunoglobulin family and a glycoprotein enriched on the surface of tumor cells, promotes invasion, metastasis, and growth and survival of malignant cells and confers resistance to some chemotherapeutic drugs. However, the molecular mechanisms underlying the actions of EMMPRIN are not fully understood. In this study we sought to determine whether EMMPRIN contributes to the malignant phenotype of breast cancer by inhibiting anoikis, a form of apoptosis induced by loss or alteration of ...
Big Science in Little Rhody
Jennifer Sanders PhD05, assistant professor of pediatrics (research) and a Rhode Island Hospital researcher, described her findings that administering the chemical rapamycin in a critical three-week window can reduce cancerous lesions in the liver. Her work in the COBRE for Cancer Research and Development has traced the molecular mechanisms underlying the effect of a pathway called mTOR. The hope is inhibition of mTOR, or its downstream effectors, may be a chemopreventive strategy against hepatocellular carcinoma.. In the COBRE for Cancer Signaling Networks, Richard Freiman, PhD, associate professor of medical science, is elucidating molecular pathways hes linked to ovarian cancer. His team has found that decreasing the levels of the protein Notch3 reduces the levels of a particular collagen protein in ovarian cancer cells. That, in turn, reduces the cells ability to resist cell death through a process called anoikis. We are presently testing a number of biological and small molecule ...
JCI - RASA1-dependent cellular export of collagen IV controls blood and lymphatic vascular development
In this study we show that RASA1 has what we believe to be a previously unappreciated critical function in the export of collagen IV from ECs during developmental angiogenesis. In the absence of RASA1, collagen IV is retained in the ER of ECs, leading to their apoptotic death as a result of ER stress and anoikis. The chemical chaperone 4PBA rescued ER retention of collagen IV, EC apoptosis, and BV hemorrhage in induced RASA1-deficient embryos. This finding strongly supports the notion that retention of collagen IV in the ER in the absence of RASA1 is a consequence of impaired protein folding. Further mechanistic studies indicated that loss of RASA1 within ECs leads to dysregulated Ras/MAPK signaling, which results in an increased abundance of several ER-resident enzymes that carry out posttranslational modifications of collagen IV that are known to regulate folding and ER export of this protein (36, 37). Most notable among these are P3H, P4H, and PLOD enzymes, of which there are 3 different ...
Nether Update out today on Java | Minecraft
elements no longer contain values stretching over multiple 64-bit fields. If number of bits per block is not power of two (i.e. single 64-bit value cant fill whole number of blockstates) some bits will not be used. For example, if single block state takes 5 bits, highest 4 bits of every 64-bit field will be unused. That also means slight increase in storage size (in case of 5 bits, from 320 to 342 64-bit fields).. ...
Faceoff (Ran Shani Mix / 16 Bit Lolitas Edit) - Remixes CD2, слушать бесплатно
101.ru: Faceoff (Ran Shani Mix / 16 Bit Lolitas Edit) слушать онлайн в хорошем качестве на 101.ru и другие треки исполнителя 16 Bit Lolitas
Checkdisk Fails at reboot (NTFS Dirty Bit set)
I am trying to run defrag but it tells me that the NTFS Dirty Bit is set. So I scheduled chechdisk to run at next boot (but it fails). How can I reset the NTFS Dirty Bit without using chkdisk or...
Little Bits Review
When I watched the TED talk on Little Bits, I knew I was going to have to get a set for my son. Little Bits are intended for children 8 to ∞.
A little bit of Kaos: A larger car play mat quilt
Am I happy with it? Mostly, I am not happy with the way the checks sit in the shunting yard, all a bit wonky. But I am not going to un-stitch .. I have un-stitched enough ...
Our 1 1/4 year old Shih Poo had a bit of a scary episode yesterday. She came in from outside shaking, dry heaving, and
Our 1 1/4 year old Shih Poo had a bit of a scary episode yesterday. She came in from outside shaking, dry heaving, and - Answered by a verified Dog Specialist
A bit of help, please
Hello, Ive installed the newest version of slackware, and Im not very good at working the system. I have two questions... My screen size is set at 6
Bit Master MP1026B- Anritsu Taiwan
MP1026B 眼圖分析儀, 掌上型、堅固耐用的解決方案,能夠對數據傳輸率為0.1到12.5Gbps的數據執行眼圖量測
Anoikis; and, in BLT2-overexpressing PWR-1E non-malignant prostate cells, 12(S)-HETE diminish anoikis-induced apoptosis. ith ... cascade following detachment confers anoikis resistance in prostate cancer cells". Journal of Biological Chemistry. 288 (42): ...
Patient derived xenograft
Zvibel I, Smets F, Soriano H (2002). "Anoikis: roadblock to cell transplantation?". Cell Transplantation. 11 (7): 621-30. doi: ... single-cell suspensions subject surviving cells to harsh chemical or mechanical forces that may sensitize cells to anoikis, ...
... contributes to tumor growth and protects cells from anoikis, a form of programmed cell death induced when contact- ... Terada LS, Nwariaku FE (March 2011). "Escaping Anoikis through ROS: ANGPTL4 controls integrin signaling through Nox1". Cancer ... March 2011). "Angiopoietin-like 4 protein elevates the prosurvival intracellular O2(-):H2O2 ratio and confers anoikis ...
2002). "Hp95 promotes anoikis and inhibits tumorigenicity of HeLa cells". Oncogene. 21 (44): 6801-8. doi:10.1038/sj.onc.1205849 ...
Yamaki N, Negishi M, Katoh H (August 2007). "RhoG regulates anoikis through a phosphatidylinositol 3-kinase-dependent mechanism ... protection from anoikis and regulation of the neutrophil NADPH oxidase. As with all small G proteins RhoG is able to signal to ...
Eukaryotic translation elongation factor 1 alpha 1
... or anoikis. Though it has not been observed to localize to the cell membrane, it can be found in the outer cell surface. Its ... "Eukaryotic translation elongation factor 1A induces anoikis by triggering cell detachment". The Journal of Biological Chemistry ...
"Hepatitis B virus X protein confers resistance of hepatoma cells to anoikis by up-regulating and activating p21-activated ... "Klotho endows hepatoma cells with resistance to anoikis via VEGFR2/PAK1 activation in hepatocellular carcinoma". PLOS ONE. 8 (3 ... "N-acetylglucosaminyltransferase V confers hepatoma cells with resistance to anoikis through EGFR/PAK1 activation". Glycobiology ...
Frisch SM (2000). "Evidence for a function of death-receptor-related, death-domain-containing proteins in anoikis". Curr. Biol ...
November 23, 2012). "CCN2 inhibits lung cancer metastasis through promoting DAPK-dependent anoikis and inducing EGFR ...
Perineuronal net Interstitium Anoikis Theocharis AD, Skandalis SS, Gialeli C, Karamanos NK (February 2016). "Extracellular ...
"CUB domain-containing protein 1 is a novel regulator of anoikis resistance in lung adenocarcinoma". Molecular and Cellular ...
Cleavage can cause cell death by anoikis and release alarmins from the ECM inducing inflammation. Fragments of fibronectin can ...
"ERK-regulated αB-crystallin induction by matrix detachment inhibits anoikis and promotes lung metastasis in vivo". Oncogene. 34 ...
Programmed cell death
Other forms of programmed cell death include anoikis, almost identical to apoptosis except in its induction; cornification, a ... Anoikis Apoptosis-inducing factor Apoptosis versus Pseudoapoptosis Apoptosome Apoptotic DNA fragmentation Autolysis (biology) ...
2004). "CEACAM6 gene silencing impairs anoikis resistance and in vivo metastatic ability of pancreatic adenocarcinoma cells". ...
... sensitized MDA-MB231 and HBC4 to anoikis, i.e., upon treatment with U0126, cells deprived of anchorage entered apoptosis ... Loss of contact with substratum triggers apoptosis in many normal cell types, a phenomenon termed anoikis. ... inhibitors restore anoikis sensitivity in human breast cancer cell lines with a constitutively activated extracellular- ...
"The HIV-1 vpr protein induces anoikis-resistance by modulating cell adhesion process and microfilament system assembly". Cell ...
Biology portal Anoikis Apaf-1 Apo2.7 Apoptotic DNA fragmentation Atromentin induces apoptosis in human leukemia U937 cells. ...
Some such forms of programmed cell death are anoikis, almost identical to apoptosis except in its induction; cornification, a ...
Matarrese P, Conti L, Varano B, Gauzzi MC, Belardelli F, Gessani S, Malorni W (2000). "The HIV-1 vpr protein induces anoikis- ...
2007). "Functional role and oncogene-regulated expression of the BH3-only factor Bmf in mammary epithelial anoikis and ... activated by anoikis". Science. 293 (5536): 1829-32. doi:10.1126/science.1062257. PMID 11546872. "Entrez Gene: BMF Bcl2 ...
... activated by anoikis". Science. United States. 293 (5536): 1829-32. doi:10.1126/science.1062257. ISSN 0036-8075. PMID 11546872 ... activated by anoikis". Science. 293 (5536): 1829-32. doi:10.1126/science.1062257. PMID 11546872. S2CID 5638023. Fuhrmann JC, ...
... activated by anoikis". Science. 293 (5536): 1829-32. Bibcode:2001Sci...293.1829P. doi:10.1126/science.1062257. PMID 11546872. ...
Silenced expression of GPR56 in HeLa cells enhanced apoptosis and anoikis, but suppressed anchorage-independent growth and cell ...
... causes anoikis resistance, chemoresistance and poor prognosis in ovarian cancer". Oncotarget. 7 (30): 47620-47636. doi:10.18632 ...
"Calreticulin promotes cell motility and enhances resistance to anoikis through STAT3-CTTN-Akt pathway in esophageal squamous ...
Uehara N, Matsuoka Y, Tsubura A (February 2008). "Mesothelin promotes anchorage-independent growth and prevents anoikis via ...
Circulating tumor cell
In general, CTCs are anoikis-resistant, which means that they can survive in the bloodstream without attaching to a substrate. ...
Indeed, TBX3 can bypass cellular senescence, apoptosis and anoikis as well as promote uncontrolled cell proliferation, tumor ...
Class III β-tubulin
"TUBB3/βIII-Tubulin Acts through the PTEN/AKT Signaling Axis to Promote Tumorigenesis and Anoikis Resistance in Non-Small Cell ...
Anoikis mechanisms. - PubMed - NCBI
Anoikis mechanisms.. Frisch SM1, Screaton RA.. Author information. 1. The Burnham Institute, 10901 North Torrey Pines Road, La ... Anoikis is defined as apoptosis that is induced by inadequate or inappropriate cell-matrix interactions. It is involved in a ... The central problem of anoikis is to understand how integrin-mediated cell adhesion signals control the apoptotic machinery. In ... particular, the initiation of the caspase cascade in anoikis remains to be explained. ...
Anoikis - Wikipedia
The word "anoikis" was coined by Frisch and Francis in a paper published in the Journal of Cell Biology in 1994. "Anoikis", in ... Given that FLIP is an inhibitor of anoikis, and that reducing FLIP can sensitize metastatic cells to anoikis, Mawji et al. ... Anoikis is a form of programmed cell death that occurs in anchorage-dependent cells when they detach from the surrounding ... When cells are detached from the ECM, there is a loss of normal cell-matrix interactions, and they may undergo anoikis. However ...
NIOSHTIC-2 Publications Search - 20042964 - Nitrosothiol signaling in anoikis resistance and cancer metastasis.
Mutant B-RAF mediates resistance to anoikis via Bad and Bim. - PubMed - NCBI
Normal cells undergo anoikis when they lose adhesion to or encounter an inappropriate extracellular matrix. By contrast, ... Depletion of Bim together with Bad has an additive effect on protecting B-RAF knockdown cells from anoikis. Together, our data ... Mutant B-RAF mediates resistance to anoikis via Bad and Bim.. Boisvert-Adamo K1, Aplin AE. ... Increased Bim(EL) levels induce apoptosis in suspended cells and are required for anoikis in B-RAF-depleted cells. ...
Anoikis - Ganfyd
JCI - ATF4-dependent induction of heme oxygenase 1 prevents anoikis and promotes metastasis
These results establish HO-1 as a mediator of ATF4-dependent anoikis resistance and tumor metastasis and suggest ATF4 and HO-1 ... ATF4-dependent induction of heme oxygenase 1 prevents anoikis and promotes metastasis. ... ATF4-dependent induction of heme oxygenase 1 prevents anoikis and promotes metastasis. ... and reconstitution of ATF4 or HO-1 expression in ATF4-deficient cells blocked anoikis and rescued tumor lung colonization. HO-1 ...
Pressure shift mediated anoikis of endothelial cells in the flow field in vitro
... anoikis). As the negative pressure is thought to play a role in the anoikis process, these results have implications for both ... a form of cell death known as anoikis. In this study, we set levels of pressure(negative and positive pressure) loaded ECs ... anoikis). As the negative pressure is thought to play a role in the anoikis process, these results have implications for both ... Hu, J. , Zhang, E. , Wu, J. , Xu, W. , Chen, H. , Shi, Y. and Guo, Y. (2010) Pressure shift mediated anoikis of endothelial ...
negative regulation of anoikis Antibodies | Invitrogen ...
anoikis | Cell Physiology
NIOSHTIC-2 Publications Search - 20043481 - Monosaccharide digitoxin derivative sensitize human non-small cell lung cancer...
Suppression of anoikis resistance by novel molecular therapies would greatly benefit treatment strategies for metastatic ... Advanced stage cancers acquire anoikis resistance which provides metastatic potential to invade and form tumors at distant ... In addition, D6-MA also targeted Mcl-1 degradation causing an increased anoikis in A549 lung cancer cells. Anoikis sensitizing ... Suppression of anoikis resistance by novel molecular therapies would greatly benefit treatment strategies for metastatic ...
Tumor suppressor protein kinase Chk2 is a mediator of anoikis of intestinal epithelial cells. | Sigma-Aldrich
... efficiently triggered anoikis of ras-transformed cells. Thus, oncogenic ras can prevent Chk2 from triggering anoikis even when ... a known inhibitor of anoikis, remain anoikis-resistant in response to enforced Chk2 upregulation. By contrast, drugs, such as ... Tumor suppressor protein kinase Chk2 is a mediator of anoikis of intestinal epithelial cells.. [Byong Hoon Yoo, Alexander ... We conclude that Chk-2 is an important novel component of anoikis-promoting machinery of intestinal epithelial cells. ...
CCN2 inhibits lung cancer metastasis through promoting DAPK-dependent anoikis and inducing EGFR degradation. | Sigma-Aldrich
CCN2 inhibits lung cancer metastasis through promoting DAPK-dependent anoikis and inducing EGFR degradation.. [C-C Chang, M-H ... In this study, we investigate the role of CCN2 in anoikis, a form of programmed cell death that is critical in suppressing ... which leads to anoikis. Overall, our findings provide evidence validating the use of CCN2 as an anti-metastatic therapy in lung ...
Abstract 2856: Inhibition of glycolysis sensitizes cancer cells to metformin-induced anoikis | Cancer Research
Abstract 2856: Inhibition of glycolysis sensitizes cancer cells to metformin-induced anoikis. Yong Yi and Zhi-Xiong Jim Xiao ... Inhibition of glycolysis sensitizes cancer cells to metformin-induced anoikis. [abstract]. In: Proceedings of the 107th Annual ... Abstract 2852: CITED2, an emerging regulator in hypoxia- and anoikis- mediated cancer cell growth ... Abstract 2856: Inhibition of glycolysis sensitizes cancer cells to metformin-induced anoikis ...
V-ATPase Inhibition Regulates Anoikis Resistance and Metastasis of Cancer Cells | Molecular Cancer Therapeutics
In fact, we report here, that archazolid induces anoikis in invasive urinary and breast cancer cells. Anoikis is provoked by a ... 5C), suggesting a role for ROS in anoikis induction. The mechanisms leading to archazolid induced anoikis and counter ... Archazolid impairs anchorage-independent growth and induces anoikis in invasive cancer cells. To start with, anoikis resistance ... In sum, we demonstrate that archazolid induces anoikis in highly invasive tumor cells (Supplementary Fig. S10). Anoikis ...
V-ATPase Inhibition Regulates Anoikis Resistance and Metastasis of Cancer Cells | Molecular Cancer Therapeutics
Anoikis resistance and archazolid action on anoikis resistant cancer cells. ... V-ATPase Inhibition Regulates Anoikis Resistance and Metastasis of Cancer Cells. Christina M. Schempp, Karin von Schwarzenberg ... V-ATPase Inhibition Regulates Anoikis Resistance and Metastasis of Cancer Cells. Christina M. Schempp, Karin von Schwarzenberg ... V-ATPase Inhibition Regulates Anoikis Resistance and Metastasis of Cancer Cells. Christina M. Schempp, Karin von Schwarzenberg ...
Figure 4 | Prolonged Nitric Oxide Exposure Enhances Anoikis Resistance and Migration through Epithelial-Mesenchymal Transition...
Prolonged Nitric Oxide Exposure Enhances Anoikis Resistance and Migration through Epithelial-Mesenchymal Transition and ... c) Anoikis susceptibility of H23, H292, H460, and A549 lung cancer cells was determined by anoikis assay. (d) The relative cell ... Nitric oxide mediated caveolin-1 upregulation, anoikis resistance and increase migration. (a) Cells were exposed to DETA ... Prolonged Nitric Oxide Exposure Enhances Anoikis Resistance and Migration through Epithelial-Mesenchymal Transition and ...
Hypoxia-Inducible Factor 1α Mediates Anoikis Resistance via Suppression of α5 Integrin | Cancer Research
A 4- to 5-fold increase of anoikis was detected in AGS KD cells compared with control cells. B, anoikis of AGS KD and SCR cells ... Effects of HIF-1α inhibition on anoikis. For induction of anoikis, AGS cells were cultivated on polyHEMA-coated dishes and ... Both variables revealed a significant induction of anoikis in 2ME2-treated cells, confirming enhanced susceptibility to anoikis ... effect of DPI on anoikis. AGS KD cells were treated for 24 h with 5 μmol/L DPI, and anoikis was quantitated by activation of ...
Novel small RNA expression libraries uncover hsa-miR-30b and hsa-miR-30c as important factors in anoikis resistance - Research...
... anoikis). Importantly, we demonstrated that the acquisition of anoikis resistance via these miRNAs is achieved through down- ... Novel small RNA expression libraries uncover hsa-miR-30b and hsa-miR-30c as important factors in anoikis resistance. Moreno- ... small RNAs, functional screens, libraries, miR-30b/c, anoikis, INDUCED APOPTOSIS, DOWN-REGULATION, NONCODING RNAS, CELL-DEATH, ...
Marine Drugs | Free Full-Text | Marine Bacterial Polysaccharide EPS11 Inhibits Cancer Cell Growth via Blocking Cell Adhesion...
Moreover, we showed that EPS11 induces apoptosis of A549 cells through stimulating βIII-tubulin associated anoikis: (i) EPS11 ... Tumor cells that acquire metastatic potential have developed resistance to anoikis, a cell death process, after detachment from ... marine bacterial polysaccharide EPS11 which exerts its cytotoxic effects through affecting cancer cell adhesion and anoikis. ... cell lung carcinoma treatment via blocking filiform structure mediated adhesion and stimulating βIII-tubulin associated anoikis ...
16-Hydroxycleroda-3,13-dien-15,16-olide induces anoikis in human renal | OTT
Mitogen-activated Protein/Extracellular Signal-regulated Kinase Kinase (MEK) Inhibitors Restore Anoikis Sensitivity in Human...
PD98059 Renders MDA-MB231 Cells Anoikis Sensitive, But Induction of Anoikis Sensitivity in HBC4 Cells Requires Further Addition ... Induction of Anoikis Sensitivity in MDA-MB231 and HBC4 Cells Requires Concurrent Inhibition of ERK and p70S6K Pathways.. The ... This phenomenon resembles anoikis, a form of apoptosis that occurs in various cell types upon detachment from the extracellular ... Anoikis is an important physiological mechanism to prevent ectopic survival of displaced cells, and its strict control is ...
Mcl-1 Is Required for Melanoma Cell Resistance to Anoikis | Molecular Cancer Research
Mcl-1 Is Required for Melanoma Cell Resistance to Anoikis. Karen Boisvert-Adamo, Whitney Longmate, Ethan V. Abel and Andrew E. ... Mcl-1 Is Required for Melanoma Cell Resistance to Anoikis. Karen Boisvert-Adamo, Whitney Longmate, Ethan V. Abel and Andrew E. ... Mcl-1 Is Required for Melanoma Cell Resistance to Anoikis. Karen Boisvert-Adamo, Whitney Longmate, Ethan V. Abel and Andrew E. ... Anoikis is a form of apoptosis induced by loss of adhesion or adhesion to an inappropriate extracellular matrix (1). The ...
Tyrosine receptor kinase B silencing inhibits anoikis‑resistance and improves anticancer efficiency of sorafenib in human renal...
Anoikis is a specific type of apoptosis induced by loss of cell adhesion or inappropriate cell adhesion (8). Anoikis plays a ... Anoikis is a specific type of apoptosis that plays a vital physiological role in regulating tissue homoeostasis. Anoikis- ... Anoikis-resistance inhibits detachment-induced apoptosis, promoting proliferation and invasion in ACHN cells. Anoikis-resistant ... TrkB silencing enhances anticancer efficiency of sorafenib in anoikis-resistant ACHN cells. (A) Anoikis-resistant ACHN cells (5 ...
Oncogenic Ras Blocks Anoikis by Activation of a Novel Effector Pathway Independent of Phosphatidylinositol 3-Kinase | Molecular...
Oncogenic Ras Blocks Anoikis by Activation of a Novel Effector Pathway Independent of Phosphatidylinositol 3-Kinase. Aidan ... Oncogenic Ras Blocks Anoikis by Activation of a Novel Effector Pathway Independent of Phosphatidylinositol 3-Kinase ... We conclude that a PI3K- and RalGEF-independent Ras effector(s) likely cooperates with Raf to confer anoikis resistance upon ... Oncogenic Ras Blocks Anoikis by Activation of a Novel Effector Pathway Independent of Phosphatidylinositol 3-Kinase ...
Nuclear p120-catenin regulates the anoikis resistance of mouse lobular breast cancer cells through Kaiso-dependent Wnt11...
Anoikis assay and colony formation assay. Anoikis resistance was determined and quantified as described previously (Derksen et ... Wnt11 regulates RhoA-dependent anoikis resistance in mILC. (A) Knockdown of Wnt11 in mILC-1 Wnt11-iKD cells reduces anoikis ... D) Rho controls anoikis resistance of mILC cells. Inhibition of Rho by cell-permeable C3 transferase leads to inhibition of ... Using anoikis-resistant mILC cell lines we now identify (candidate) Kaiso target genes including Wnt11 in anchorage-independent ...
Foretinib (GSK1363089), an Orally Available Multikinase Inhibitor of c-Met and VEGFR-2, Blocks Proliferation, Induces Anoikis,...
Foretinib induces anoikis through a 2-step process. A, Hoechst 33342 staining of detached cells. CaOV3 cells were pretreated ... The inhibitor induces anoikis and blocks many functions important for ovarian cancer metastasis including, c-Met signaling, ... Our data suggest that anoikis induction contributes to the potent antitumor effects of the inhibitor. Characterization of the ... Consistent with a mechanism of anoikis, cell death occurred in 2 distinct stages; detachment followed by caspase-mediated ...
PLK1 Is Transcriptionally Activated by NF-κB during Cell Detachment and Enhances Anoikis Resistance through Inhibiting β...
... and anoikis induction is blocked, ultimately leading to tumor invasion and metastasis. Several anti-anoikis signals in cancer ... RelA modulates anoikis resistance through the PLK1/β-catenin pathway. To further explore the role of RelA in the regulation of ... PLK1 regulates anoikis resistance through β-catenin in ESCC cells. A, after SDS-PAGE, bands present only in the PBD eluents ... PLK1 regulates anoikis resistance of esophageal cancer cells through β-catenin. The polo-box domain of PLK1 was previously ...
LMO3 promotes hepatocellular carcinoma invasion, metastasis and anoikis inhibition by directly interacting with LATS1 and...
2d, e) cells after 48 h. Furthermore, through annexin V anoikis assay, we found that the knockdown of LMO3 promoted the anoikis ... Anoikis assays. 5 × 105 MHCC-97H or SMMC-7721 cells were cultured on poly-HEMA treated 12-well plates at 37 °C for 48 h. Then ... 6a, b). Meanwhile, the anoikis inhibition of Huh-7 or SNU-423 cells induced by rLMO3 protein was also abrogated by these ... LMO3 knockdown suppresses the invasion and anoikis inhibition of HCC cells in vitro. a Expression of LMO3 in HCC cell lines, ...
Membrane associated collagen XIII promotes cancer metastasis and enhances anoikis resistance | System Biosciences
Redox regulation of anoikis resistance of metastatic prostate cancer cells: key role for Src and EGFR-mediated pro-survival...
... a process commonly referred as anoikis, is emerging as a hallmark of metastatic malignancies, mainly because it can ensure ... Redox regulation of anoikis resistance of metastatic prostate cancer cells: key role for Src and EGFR-mediated pro-survival ... Anoikis sensitivity of metastatic cells is restored with antioxidant intervention or genetic manipulation of the redox-mediated ... Resistance to detachment-induced apoptosis, a process commonly referred as anoikis, is emerging as a hallmark of metastatic ...
MetastasisPathwaysEscape anoikisCells from anoikisResistant to anoikisSensitivity to anoikisDetachment-inducedMetastaticInhibits anoikisRole in anoikisSensitive to anoikisSusceptibilityExtracellularSuppressionKnockdownSuppress anoikisEnhances anoikisInhibitorIntegrinIntestinal epithelial cellsMechanisms of anoikis-resistanceAcquisition of resistance to anoikisTrkBPathwayVitroOncogenicOvarian cancerInductionNormal epithelial cellsType of apoptosis inducedInduceProgressionApoptosis that is inducedReceptorCancerMolecularDeprivation-induced apoptosisKnown as anoikisInhibition of anoikisProtection from anoikisCell death inducedDegradationUndergoTumor suppressor
- Nitrosothiol signaling in anoikis resistance and cancer metastasis. (cdc.gov)
- In this article we discuss the various roles of NO and protein nitrosylation in cancer development, with a focus on cell invasion and anoikis resistance, both of which are key determinants of cancer metastasis. (cdc.gov)
- These results establish HO-1 as a mediator of ATF4-dependent anoikis resistance and tumor metastasis and suggest ATF4 and HO-1 as potential targets for therapeutic intervention in solid tumors. (jci.org)
- CCN2 inhibits lung cancer metastasis through promoting DAPK-dependent anoikis and inducing EGFR degradation. (sigmaaldrich.com)
- In this study, we investigate the role of CCN2 in anoikis, a form of programmed cell death that is critical in suppressing cancer metastasis. (sigmaaldrich.com)
- Thus, V-ATPase inhibition is not only an interesting option to reduce cancer metastasis, but also to better understand anoikis resistance and to find choices to fight against it. (aacrjournals.org)
- Anoikis-resistance is of critical importance for metastasis of various human cancers including mRCC. (spandidos-publications.com)
- Previous investigations have implied that activation or overexpression of TrkB promoted proliferation, survival, angiogenesis, anoikis-resistance and metastasis in human cancers. (spandidos-publications.com)
- Anoikis-resistance is consequently an essential prerequisite of progression and metastasis of various human cancer types ( 10 , 11 ). (spandidos-publications.com)
- Activation of TrkB promoted tumor cell proliferation, survival, angiogenesis, epithelial-mesenchymal transition (EMT), anoikis-resistance and metastasis through regulating specific signaling pathways including phosphoinositide 3-kinases (PI3K)/Akt and MEK/ERK ( 15 - 17 ). (spandidos-publications.com)
- The inhibitor induces anoikis and blocks many functions important for ovarian cancer metastasis including, c-Met signaling, adhesion, invasion, and proliferation. (aacrjournals.org)
- In contrast, malignant cells are resistant to anoikis, which leads to enhanced survival after detachment from the supporting matrix and facilitates metastasis ( 5 ). (aacrjournals.org)
- These results suggest that Src activation may contribute to colon tumor progression and metastasis in part by activating Akt-mediated survival pathways that decrease sensitivity of detached cells to anoikis. (elsevier.com)
- Reduced sensitivity to anoikis appears to be an important hallmark of oncogenic transformation, particularly in the process of metastasis. (nih.gov)
- Finally, endosomal integrin signalling contributes to cancer-related processes such as anoikis resistance, anchorage independence and metastasis. (vtt.fi)
- Among the steps that occur during cancer cell metastasis, escaping apoptosis (i.e., anoikis resistance) while detaching from the extracellular matrix or neighboring cells at the primary sites and circulating in transit to a distant location is of utmost importance. (biomedcentral.com)
- There is evidence suggesting that CD147, an adhesion molecule associated with survival of cells in tumor metastasis and cell-cell contacts, plays an important role in resistance to anoikis. (biomedcentral.com)
- Understanding of the role of HAb18G/CD147 cell-cell contacts in anoikis resistance may help in understanding the survival of cells in anchorage-independent growth, such as cells in tumor metastasis and suspension culture produced for biomedical engineering. (biomedcentral.com)
- Our study suggested that CD24 may play an important role in the development of anoikis resistance and CD24 can be used as a new therapeutic target to induce anoikis and inhibit metastasis in ovarian cancer . (bvsalud.org)
- In order for metastasis to occur, cancer cells have to overcome anoikis. (eurekalert.org)
- As V-ATPase inhibitors have shown to prevent invasion of tumor cells and are able to induce apoptosis, we proposed that V-ATPase inhibition induces anoikis-related pathways in invasive cancer cells. (aacrjournals.org)
- To study the biochemical basis for induction of anoikis sensitivity, we examined the effects of the MEK inhibitors on ERK and p70 S6K pathways in anchored versus nonanchored cells. (aacrjournals.org)
- Furthermore, TrkB silencing caused apoptosis, inhibited proliferation, retarded invasion as well as improved anticancer efficiency of sorafenib in anoikis-resistant ACHN cells through inactivation of PI3K/Akt and MEK/ERK pathways. (spandidos-publications.com)
- Anoikis inducted cell deaths dominates with two differing pathways - intrinsic and extrinsic pathway. (labroots.com)
- In fact, there are several primary contributors in the emergence of androgen-independent metastatic prostate cancer such as activation of survival pathways, including apoptosis, suppression of anoikis resistance, (13) and increased neovascularization. (thefreedictionary.com)
- Moreover, our results suggest that the pathways regulating anoikis resistance and chemotherapy resistance might involve the action of different mediators. (biomedcentral.com)
- Since the general acquisition of apoptosis resistance would affect both de-adhesion and chemotherapy-induced cell death, we investigated whether acquisition of anoikis resistance conferred general resistance to other apoptotic inducers or was independent of these other apoptotic pathways. (biomedcentral.com)
- In this study we sought to determine whether EMMPRIN contributes to the malignant phenotype of breast cancer by inhibiting anoikis, a form of apoptosis induced by loss or alteration of cell-cell or cell-matrix anchorage, and to explore the signaling pathways involved. (elsevier.com)
- Thus, we show that TGF-beta has variable effects on anoikis in colon cancer cell lines that likely reflects the effects of concurrent gene mutations in the cancer cells and the activation state of the signaling pathways controlled by these genes. (nih.gov)
- Several pathways have been implicated in the suppression of anoikis, however, the events which take place proximal to the integrin receptors remain unclear. (nih.gov)
- However, the signaling pathways that regulate p53-dependent anoikis are largely unknown. (biomedcentral.com)
- The investigators then dissected different pathways, including a phenomenon called anoikis, which prevents epithelial cells from changing into other cell types by causing them to commit suicide. (eurekalert.org)
- The ability of transformed epithelial cells to initiate the metastatic cascade relies on their ability to escape anoikis, a default program of apoptosis induction following loss of integrin anchoring to the extracellular matrix. (aacrjournals.org)
- The reasons for this are unknown: one theory is that overexpression of the NTRK1 receptor for nerve growth factor (see neurotrophin) somehow enables cells to escape anoikis. (oup.com)
- However, the mechanisms that enable this subset of normal HMECs to escape anoikis and survive in suspension remain unexplored. (beds.ac.uk)
- They escape anoikis due to an upregulation in their energy metabolism. (els.net)
- Carcinoma cells are epithelial cells gone bad and have learned to act like neurons, inappropriately activating TrkB signaling to escape anoikis. (redorbit.com)
Cells from anoikis8
- Depletion of Bim together with Bad has an additive effect on protecting B-RAF knockdown cells from anoikis. (nih.gov)
- We found that enforced downregulation of Chk2 protects intestinal epithelial cells from anoikis. (sigmaaldrich.com)
- The serine/threonine kinase B-RAF is mutated in 50% to 70% of melanomas and protects melanoma cells from anoikis, a form of apoptosis induced by lack of adhesion or adhesion to an inappropriate matrix. (aacrjournals.org)
- We determined that oncogenic versions of H-, K-, and N-Ras, as well as the Ras-related proteins TC21 and R-Ras, protected RIE-1 cells from anoikis. (asm.org)
- PLK1 protects esophageal carcinoma cells from anoikis through modulation of β-catenin protein levels by inhibiting their degradation. (aacrjournals.org)
- Elevated expression of SKP2 protected cancer cells from anoikis, and this effect was mediated, at least in part, by the phosphoinositidyl 3-kinase-Akt pathway. (aacrjournals.org)
- These results indicated that expression of EMMPRIN protects cancer cells from anoikis and that this effect is mediated at least in part by a MAP kinase-dependent reduction of Bim. (elsevier.com)
- In addition we identify also a PKA/Src mechanism capable to protect cancer cells from anoikis. (uni.lu)
Resistant to anoikis4
- It seems that TrkB could make tumor cells resistant to anoikis by activating phosphatidylinositol 3-kinase (PI3K) signaling cascade. (wikipedia.org)
- certain cells (e.g., epithelial and endothelial cells) are more resistant to anoikis. (thefreedictionary.com)
- Metastatic cells are resistant to anoikis and often have increased levels of the death receptor-inhibiting protein FLIP. (thefreedictionary.com)
- We found that in the absence of attachment, human breast carcinoma cells expressing high levels of EMMPRIN formed less compact aggregates with larger surface area and less fibronectin matrix assembly, had higher viability, and were resistant to anoikis. (elsevier.com)
Sensitivity to anoikis3
- Furthermore, we observed that the accumulation of Bim, a proapoptotic BH3-only protein, was reduced in EMMPRIN-expressing cells and that silencing of EMMPRIN expression elevated Bim protein levels and enhanced cellular sensitivity to anoikis. (elsevier.com)
- We report herein that differentiated IECs exhibit a greater sensitivity to anoikis than undifferentiated ones. (biomedcentral.com)
- When researchers at the University of Colorado Cancer Center reintroduced miR-200c to aggressive, triple-negative breast cancer cells, these cells regained sensitivity to anoikis and self-destructed. (redorbit.com)
- We further found that, unlike nonmalignant intestinal epithelial cells whose anoikis is triggered by detachment-induced Chk2 upregulation, intestinal epithelial cells carrying oncogenic ras, a known inhibitor of anoikis, remain anoikis-resistant in response to enforced Chk2 upregulation. (sigmaaldrich.com)
- Our data revealed that anoikis-resistant ACHN cells presented with tolerance to detachment-induced apoptosis, excessive proliferation and aggressive invasion, accompanied by upregulation of TrkB expression in contrast to parental cells. (spandidos-publications.com)
- Resistance to detachment-induced apoptosis, a process commonly referred as anoikis, is emerging as a hallmark of metastatic malignancies, mainly because it can ensure anchorage-independent growth and survival during organ colonization. (nih.gov)
- In this study, we addressed the potential role of Src activation to a specific aspect of tumor cell survival, resistance to detachment-induced apoptosis (anoikis). (elsevier.com)
- When deprived of anchorage, normal epithelial cells undergo detachment-induced apoptosis, or anoikis, irrespective of the presence of growth factors ( Gilmore, 2005 ). (rupress.org)
- However, metastatic tumor cells may escape from anoikis and invade other organs. (wikipedia.org)
- showed that anisomycin can sensitize metastatic epithelial cells to anoikis and reduce circulating tumor cell implantation in vivo. (wikipedia.org)
- In related work, Schimmer's team showed that FLIP levels are higher in metastatic cells than non-metastatic cells, and that reducing FLIP levels using RNAi (RNA Interference) or other small molecule inhibitors of FLIP can sensitize metastatic cells to anoikis. (wikipedia.org)
- Given that FLIP is an inhibitor of anoikis, and that reducing FLIP can sensitize metastatic cells to anoikis, Mawji et al. (wikipedia.org)
- Here, we have shown that activating transcription factor 4 (ATF4), a master transcriptional effector of the ISR, protects transformed cells against anoikis - a specialized form of apoptosis - following matrix detachment and also contributes to tumor metastatic properties. (jci.org)
- Advanced stage cancers acquire anoikis resistance which provides metastatic potential to invade and form tumors at distant sites. (cdc.gov)
- Suppression of anoikis resistance by novel molecular therapies would greatly benefit treatment strategies for metastatic cancers. (cdc.gov)
- In this study, we investigated the anoikis sensitizing effect of D6-MA compared with digitoxin to identify their anti-metastatic mechanism of action. (cdc.gov)
- These results identify a novel cardiac glycoside (CG) sensitizing anoikis mechanism and provide a promising anti-metastatic target for lung cancer therapy. (cdc.gov)
- Resistance of invasive cells to anoikis, a particular type of apoptosis induced by loss of cell-matrix contact, is a major prerequisite for their metastatic spread. (aacrjournals.org)
- Inducing anoikis in metastatic cancer cells is therefore a promising therapeutic approach. (aacrjournals.org)
- We used the V-ATPase inhibitor archazolid to investigate the mechanism of anoikis induction in various metastatic cancer cells (T24, MDA-MB-231, 4T1, 5637) in vitro . (aacrjournals.org)
- Tumor cells that acquire metastatic potential have developed resistance to anoikis, a cell death process, after detachment from their primary site to the second organ. (mdpi.com)
- Anoikis sensitivity of metastatic cells is restored with antioxidant intervention or genetic manipulation of the redox-mediated pro-survival pathway, as well as exposure to a pro-oxidant environment strongly increases anoikis resistance in non-transformed prostate epithelial cells. (nih.gov)
- Hence, our results allow new insight into the aetiology of the molecular mechanisms granting anoikis resistance of metastatic cancers, opening new avenues to pharmacological intervention for antioxidant-sensitive invasive tumours. (nih.gov)
- Resistance to anoikis (matrix deprivation-induced apoptosis) is a critical component of the metastatic cascade. (cdc.gov)
- Anoikis resistance is a fundamental feature of metastatic cancer cell survival during metastatic cancer progression. (biomedcentral.com)
- Our data identify a novel signaling axis of miR-141/KLF12/Sp1/survivin in enhancing anoikis resistance and likely serves as a potential therapeutic target for metastatic ovarian cancer. (biomedcentral.com)
- Hepatocyte growth factor inhibits anoikis in head and neck squamous cell carcinoma cells by activation of ERK and Akt signaling independent of NFkappa B". The Journal of Biological Chemistry. (wikipedia.org)
- For the last call, micro RNA (miRNA) inhibits anoikis, while at the same time different miRNA marks cancer not to progress any further. (labroots.com)
- In vitro, E 2 inhibits anoikis of tuberin-null cells. (pnas.org)
- When Tsc2-null cells are injected intravenously, E 2 enhances their survival and lung colonization, and in vitro, E 2 inhibits anoikis of Tsc2-null cells. (pnas.org)
- TrkB inhibits anoikis in nasopharyngeal carcinoma cells . (bvsalud.org)
Role in anoikis3
- Our work revealed that the RelA-PLK1-β-catenin pathway plays an important role in anoikis resistance in esophageal squamous cell carcinoma (ESCC) cells. (aacrjournals.org)
- Tumor suppressor p53 is mutated in a wide variety of human cancers and plays a critical role in anoikis, which is essential for preventing tumorigenesis. (biomedcentral.com)
- p53 also plays a critical role in anoikis. (biomedcentral.com)
Sensitive to anoikis2
- Using RNA interference, we show that depletion of Mcl-1 renders mutant B-RAF melanoma cells sensitive to anoikis. (aacrjournals.org)
- Treatment of cells with a MEK inhibitor (U0126) or proteasome inhibitor (epoxomicin) also up-regulated Bim accumulation and rendered cells more sensitive to anoikis. (elsevier.com)
- RNA interference and overexpression experiments demonstrate that Bad contributes to the susceptibility of B-RAF-depleted cells to anoikis. (nih.gov)
- c) Anoikis susceptibility of H23, H292, H460, and A549 lung cancer cells was determined by anoikis assay. (hindawi.com)
- HIF-1α-deficient cells displayed significantly increased anoikis susceptibility due to up-regulated α5 integrin. (aacrjournals.org)
- Our functional analysis revealed a markedly reduced ability of HIF-1α-deficient cells to evade anoikis, and we provide experimental evidence for a causal role of α5 integrin in restoring anoikis susceptibility. (aacrjournals.org)
- Thus, susceptibility of the p70 S6K pathway to MEK inhibitors appeared to be an important determinant of anoikis sensitivity. (aacrjournals.org)
- The susceptibility of cells to anoikis controls their numbers during development and normal homeostasis. (aacrjournals.org)
- whereas decreased Src expression in HT29 cells (of high Src expression and activity) by transfection with anti-sense Src expression vectors increases susceptibility to anoikis. (elsevier.com)
- PD173955, a Src family-specific tyrosine kinase inhibitor, increases the susceptibility of HT29 cells to anoikis in a dose- and time-dependent manner. (elsevier.com)
- Anoikis is a form of programmed cell death that occurs in anchorage-dependent cells when they detach from the surrounding extracellular matrix (ECM). (wikipedia.org)
- In squamous cell carcinoma, researchers have found that anoikis resistance can be induced through hepatocyte growth factor (HGF) activating BOTH extracellular signalling-receptor kinase (ERK) and PI3K. (wikipedia.org)
- Normal cells undergo anoikis when they lose adhesion to or encounter an inappropriate extracellular matrix. (nih.gov)
- Previously, we demonstrated that B-RAF and downstream mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) signaling are necessary for protection from anoikis in mutant B-RAF-expressing melanoma cells. (nih.gov)
- We present these data here to suggest that the negative pressure might be another important factor beyond velocity and shear stress in biomechanical impairment on ECs, then to trigger the apoptosis with the extracellular matrix (ECM) detachment (anoikis). (scirp.org)
- Resistance of carcinoma cells to anoikis, apoptosis that is normally induced by detachment of nonmalignant epithelial cells from the extracellular matrix, is thought to be critical for carcinoma progression. (sigmaaldrich.com)
- Binding of CCN2 to EGFR suppresses the phosphorylation of c-Src and extracellular signal-regulated kinase but increases the expression of death-associated protein kinase, which leads to anoikis. (sigmaaldrich.com)
- However, we observed that archazolid also induces mechanisms opposing anoikis such as degradation of BIM mediated by extracellular signal-regulated kinase (ERK), Akt and Src kinases at later time points and induction of reactive oxygen species. (aacrjournals.org)
- Mitogen-activated Protein/Extracellular Signal-regulated Kinase Kinase (MEK) Inhibitors Restore Anoikis Sensitivity in Human Breast Cancer Cell Lines with a Constitutively Activated Extracellular- regulated Kinase (ERK) Pathway 1 This work was supported by a Grant-in-Aid for Cancer Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. (aacrjournals.org)
- Anoikis is a form of apoptosis induced by loss of adhesion or adhesion to an inappropriate extracellular matrix ( 1 ). (aacrjournals.org)
- Treatment of Ras-transformed cells with the U0126 MEK inhibitor caused partial reversion to an anoikis-sensitive state, indicating that extracellular signal-regulated kinase activation contributes to inhibition of anoikis. (asm.org)
- Anoikis, first described and coined in 1994 by Frisch and Francis, spells cell death when there was a lack of attachment to the extracellular matrix (ECM). (labroots.com)
- Anoikis resistance can be induced through activation of extracellular signalling-receptor kinase (ERK) and the phosphatidylinositol 3-kinase (PI3K) signalling cascade by hepatocyte growth factor (HGF). (thefreedictionary.com)
- Since cell adhesion to the extracellular matrix acts as a survival factor that homeostatically maintains normal tissue architecture, it was tested whether acquisition of resistance to deadhesion-induced apoptosis (anoikis) in human osteosarcoma would result in resistance to chemotherapy. (biomedcentral.com)
- The term anoikis defines the type of apoptosis induced after proper adherence to the extracellular matrix (ECM) is denied[ 3 , 4 ]. (biomedcentral.com)
- Disruption of integrin-extracellular matrix interactions in normal epithelial cells induces apoptosis, a process termed anoikis. (nih.gov)
- Under anchorage-independent conditions, PTEN also induces anoikis, a form of apoptosis that occurs when cells are dissociated from the extracellular matrix, which is enhanced in conjunction with low serum culture conditions. (elsevier.com)
- Two new papers from the lab of Zach Schafer, Coleman Assistant Professor of Cancer Biology at the University of Notre Dame, offer insights into how breast cancer cells avoid anoikis, which is cell death induced by detachment from the extracellular matrix (ECM). (news-medical.net)
- PTEN appears to play particularly important roles in regulating anoikis (apoptosis of cells after loss of contact with extracellular matrix) and cell migration. (biologists.org)
- We have examined endogenous Bax in epithelial cells undergoing anoikis, a physiologically relevant form of apoptosis that occurs when normal cells lose contact with the extracellular matrix (ECM). (pubmedcentralcanada.ca)
- We also evaluated the effects of TGF-β signaling on advanced colorectal cancer, particularly on the acquisition of resistance to anoikis or cell death induced by inappropriate cell-cell or cell-extracellular matrix attachment. (vanderbilt.edu)
- Hence, our data argue for a pivotal role for HIF-1α in anoikis control via suppression of α5 integrin. (aacrjournals.org)
- The general thumb rule in which cancer cells outsmarts anoikis: stimulation of prosurvival actors and suppression of death signals. (labroots.com)
- Caspase-8 inhibition through FLICE-inhibitory protein (FLIP) overexpression puts a stop to anoikis, as does suppression of Bim and BMF since both proteins are associated with cytoskeleton and combat the antiapoptotic Bcl-2 protein. (labroots.com)
- On the other hand, transfection of a dominant negative form of FAK (FRNK) failed to reverse the suppression of anoikis by ILK. (nih.gov)
- These findings suggest that ILK plays a major role in the suppression of anoikis. (nih.gov)
- Therefore, we investigated whether α2β1, α3β1, α5β1, and α6β4 integrins perform differentiation state-specific roles in the suppression of IEC anoikis. (biomedcentral.com)
- This involves an earlier onset of anoikis when kept in suspension, as well as significantly greater contributions from β1 and β4 integrins in the suppression of anoikis in differentiated cells, and functional distinctions between β1 and β4 integrins in engaging both Fak and Src, or Src only, respectively. (biomedcentral.com)
- Likewise, Fak performs significantly greater contributions in the suppression of anoikis in differentiated cells. (biomedcentral.com)
- Furthermore, we provide evidence that α6β4 contributes to the suppression of anoikis in a primarily α6 subunit-dependent manner in undifferentiated cells, whereas this same integrin in differentiated cells performs significantly greater contributions in anoikis suppression than its undifferentiated state-counterpart, in addition to doing so through a dependence on both of its subunits. (biomedcentral.com)
- Our findings indicate that the suppression of human IEC anoikis implicates differentiation state-selective repertoires of integrins, which in turn results into distinctions in anoikis regulation, and sensitivity, between undifferentiated and differentiated IECs. (biomedcentral.com)
- These data further the functional understanding of the concept that the suppression of anoikis is subjected to cell differentiation state-selective mechanisms. (biomedcentral.com)
- Mcl-1 over-expression and knockdown studies in D6-MA and digitoxin exposed cells resulted in rescue and enhancement, respectively, indicating a facilitative role for decreased Mcl-1 expression in NSCLC anoikis. (cdc.gov)
- The role of PLK1 in cell anoikis resistance was examined by ectopic gene expression and siRNA-mediated knockdown. (aacrjournals.org)
- Knockdown of LMO3 suppressed the invasion and anoikis inhibition of HCC cells in vitro. (springer.com)
- Knockdown of SKP2 expression sensitized cancer cells to anoikis, and a wobble mutant of SKP2 that is resistant to SKP2 small interfering RNA can rescue this effect. (aacrjournals.org)
- Knockdown of EMMPRIN expression by RNA interference (small interfering RNA or short hairpin RNA) sensitized cancer cells to anoikis, as demonstrated by activation of caspase-3, increased DNA fragmentation, and decreased cellular viability. (elsevier.com)
- In vivo and in vitro experiments using the breast cancer cell lines MCF-7 and ZR-75-1, which expresses wild type p53, showed that tumorigenesis, colony formation, and anoikis resistance were significantly enhanced by MYBBP1A knockdown. (biomedcentral.com)
- Enforced expression of miR-141 promotes, while knockdown of miR-141 expression inhibits, cell proliferation, anchorage-independent capacity, anoikis resistance, tumor growth and peritoneal metastases of ovarian cancer cells. (biomedcentral.com)
- Additionally, we show that α2β1 and α5β1 suppress anoikis in undifferentiated cells, whereas α3β1 does so in differentiated ones. (biomedcentral.com)
- In this study, we showed that upregulation of PLK1 triggered by cell detachment enhances anoikis resistance of esophageal cancer cells by inhibiting β-catenin degradation. (aacrjournals.org)
- Another MEK inhibitor PD98059 also induced anoikis sensitivity in MDA-MB231 cells but not in HBC4 cells. (aacrjournals.org)
- However, HBC4 cells were sensitized to anoikis when PD98059 was combined with the mTOR inhibitor rapamycin. (aacrjournals.org)
- Unexpectedly, oncogenic Ras failed to activate Akt, and treatment of Ras-transformed RIE-1 cells with the LY294002 PI3K inhibitor did not affect anoikis resistance or growth in soft agar. (asm.org)
- Treatment of cells with phosphoinositidyl 3-kinase inhibitor (LY294002) and constitutively activator (insulin-like growth factor I) had significant effects on the anoikis of SKP2 RNA interference cells. (aacrjournals.org)
- In colon tumor cells with high Src activity, the PI3 kinase inhibitor LY 294002 sensitized cells to anoikis. (elsevier.com)
- The central problem of anoikis is to understand how integrin-mediated cell adhesion signals control the apoptotic machinery. (nih.gov)
- Cancer cells develop anoikis resistance by several mechanisms, including changes in integrin and matrix signaling, metabolic deregulation, and stress responses of cancer cells. (wikipedia.org)
- Ishida, K., Nagahara, H. and Kogiso, T. (2003) Cell adhesion aside from integrin system can abrogate anoikis in rat liver cells by down-regulation of FasL expression, not by activation of PI-3K/Akt and ERK signaling pathway. (scirp.org)
- Anoikis induction by archazolid was characterized by decreased c-FLIP expression and caspase-8 activation as well as reduction of active integrin-β1 and an early increase of the proapoptotic protein BIM. (aacrjournals.org)
- Together, these data suggest that PTEN effects on the P13K signaling cascade are influenced by the cell stimulatory context, and that depending on the exposure to growth factors and other exogenous stimuli such as integrin ligation, PTEN can induce cell cycle arrest, apoptosis or anoikis in breast cancer cells. (elsevier.com)
- Human (HIEC, Caco-2/15) IECs were exposed to specific antibodies that block the binding activity of integrin subunits (α2, α3, α5, α6, β1 or β4) to verify whether or not their inhibition induced anoikis. (biomedcentral.com)
Intestinal epithelial cells5
- Tumor suppressor protein kinase Chk2 is a mediator of anoikis of intestinal epithelial cells. (sigmaaldrich.com)
- In an effort to understand them we found that detachment of nonmalignant intestinal epithelial cells triggers upregulation of Chk2, a pro-apoptotic protein kinase that has never been implicated in anoikis and has been thought to kill cells mainly under the conditions compromising genome integrity. (sigmaaldrich.com)
- Chk2 can kill cells by stabilizing p53 tumor suppressor protein or via p53-independent mechanisms, and we established that Chk2-mediated anoikis of intestinal epithelial cells is p53-independent. (sigmaaldrich.com)
- We conclude that Chk-2 is an important novel component of anoikis-promoting machinery of intestinal epithelial cells. (sigmaaldrich.com)
- Regulation of anoikis in human intestinal epithelial cells (IECs) implicates differentiation state-specific mechanisms. (biomedcentral.com)
Mechanisms of anoikis-resistance2
- Anoikis-resistance is closely related to mRCC ( 12 , 13 ), while the exact mechanisms of anoikis-resistance in mRCC remain unclear. (spandidos-publications.com)
- Our study identifies a novel AMPK-PEA15 signaling axis in the anchorage-independent growth of both normal and cancerous mammary epithelial cells, suggesting that breast cancer cells may employ mechanisms of anoikis resistance already inherent within a subset of normal HMECs. (beds.ac.uk)
Acquisition of resistance to anoikis2
- Acquisition of resistance to "anoikis" facilitates the survival of cells under independent matrix-deficient conditions, such as cells in tumor progression and the production of suspension culture cells for biomedical engineering. (biomedcentral.com)
- The acquisition of resistance to anoikis, a form of apoptosis triggered by loss or alteration of cell-cell or cell-matrix anchorage, is critical for the survival of cells in tumor progression and suspension growth used in engineering. (biomedcentral.com)
- Yet, the correlation between TrkB and anoikis-resistance in mRCC has rarely been reported. (spandidos-publications.com)
- The aim of the present study was to explore the impact of TrkB on anoikis-resistance and targeted therapy in mRCC. (spandidos-publications.com)
- To study the regulation of anoikis by tyrosine kinase receptor B (TrkB) in human nasopharyngeal carcinoma lines. (bvsalud.org)
- And exogenous BDNF stimulated up-regulation TrkB and p-Akt, induced anoikis resistance. (bvsalud.org)
- Inhibiton of TrkB by K252a can induce anoikis , and may prove particularly effective in treatment of nasopharyngeal carcinoma . (bvsalud.org)
- healthy epithelial cells don't have TrkB and so are susceptible to anoikis. (redorbit.com)
- Anoikis is controlled by activation of the mitochondrial apoptotic pathway involving subfamilies of Bcl-2 proteins that differ in their activities ( 2 ). (aacrjournals.org)
- Inhibition of the NF-κB pathway restores the sensitivity of cancer cells to anoikis by downregulating PLK1/β-catenin expression. (aacrjournals.org)
- These results suggested that the RelA-PLK1-β-catenin pathway might be a potential target of therapies designed to restore the sensitivity of ESCC cells to anoikis. (aacrjournals.org)
- The inhibitors of the Hippo pathway abrogated rLMO3 protein-induced HCC cell invasion and anoikis inhibition. (springer.com)
- In addition, our data indicated that SKP2 promotes anoikis resistance through the phosphoinositidyl 3-kinase (PI3K)-Akt pathway. (aacrjournals.org)
- In contrast, restoration of KLF12 in miR-141-expressing cells significantly attenuated anoikis resistance in ovarian cancer cells via interfering with Sp1-mediated survivin transcription, which inhibits the intrinsic apoptotic pathway and is crucial for ovarian cancer cell survival, anoikis resistance and peritoneal metastases. (biomedcentral.com)
- and cell-cell contact mediated resistance to anoikis implicates PI3K pathway in a highly relevant cell model (HEK293ar). (biomedcentral.com)
- The aim of this work was to characterize alterations in metabolites of the arginine pathway, en. (biomedcentral.com)
- XEDAR as a putative colorectal tumor suppressor that mediates p53-regulated anoikis pathway. (ebi.ac.uk)
- In vitro transwell matrigel invasion assay and annexin V anoikis assay in HCC cells were conducted to investigate LMO3 related biological functions. (springer.com)
- For an in vitro model of anoikis, we cultured follicular, papillary, and anaplastic thyroid cancer cell lines on poly-HEMA-treated low-adherent plates. (cdc.gov)
- Immunofluorescence, immune transmission electron microscopy, chromatin fractionation, co-immunoprecipitation, and assays for chromatin immunoprecipitation, dual luciferase reporter, agarose-oligonucleotide pull-down, flow cytometry and cell anoikis were performed to uncover nuclear MYH9-induced β-catenin ( CTNNB1 ) transcription in vitro . (thno.org)
- Nuclear MYH9 bound to the CTNNB1 promoter through its DNA-binding domain, and interacted with myosin light chain 9, β-actin and RNA polymerase II to promote CTNNB1 transcription, which conferred resistance to anoikis in GC cells in vitro and in vivo . (thno.org)
- By contrast, oncogenic signaling in tumor cells enables resistance to anoikis, a trait that contributes to tumor progression. (nih.gov)
- Thus, oncogenic ras can prevent Chk2 from triggering anoikis even when levels of this protein kinase are elevated in cancer cells, and the use of therapeutic agents that kill cells in a Chk-2-independent, rather than Chk-2-dependent, manner could represent an efficient strategy for overcoming ras-induced anoikis resistance of these cells. (sigmaaldrich.com)
- To further assess the contribution of Raf-dependent and Raf-independent function in oncogenic Ras transformation, we evaluated the mechanism by which oncogenic Ras blocks suspension-induced apoptosis, or anoikis, of RIE-1 cells. (asm.org)
- The mechanism of inhibition by foretinib involved (a) inhibition of c-Met activation and downstream signaling, (b) reduction of ovarian cancer cell adhesion, (c) a block in migration and invasion, (d) reduced proliferation mediated by a G 2 -M cell-cycle arrest, and (e) induction of anoikis. (aacrjournals.org)
- However, the mechanisms underlying anoikis resistance in ovarian cancer are still unclear. (biomedcentral.com)
- This study examined the effect of CD24 on anoikis of ovarian cancer cells . (bvsalud.org)
- In the Molecular Cancer Therapeutics paper with Diana Cittelly, PhD as first author, the group showed that reintroducing miR-200c to ovarian cancer cells in animal models not only restarted anoikis, but also sensitized these cells to the widely used chemotherapy paclitaxel. (redorbit.com)
- Reduction of anchorage-independent colony formation and induction of anoikis by archazolid (Arch. (aacrjournals.org)
- We show that mammary-specific stochastic inactivation of conditional E-cadherin and p53 results in impaired mammary gland function during pregnancy through the induction of anoikis resistance of mammary epithelium, resulting in loss of epithelial organization and a dysfunctional mammary gland. (biologists.org)
- We show in the present study that the accumulation of an intracellular 45 kDa clusterin isoform was an early event closely associated with death of PNT1A cells caused by cell detachment followed by apoptosis induction (anoikis). (biochemj.org)
Normal epithelial cells2
- Detachment of normal epithelial cells from the ECM typically results in anoikis, which is essential for several morphogenetic and homeostatic processes, such as embryo cavitation ( 2 ), postweaning mammary gland regression ( 3 ), and elimination of epithelial cells shed into the intestinal lumen ( 4 ). (aacrjournals.org)
- Matrix detachment triggers anoikis, a form of apoptosis, in most normal epithelial cells, while acquisition of anoikis resistance is a prime requisite for solid tumor growth. (beds.ac.uk)
Type of apoptosis induced1
- Anoikis is a specific type of apoptosis induced by loss of cell adhesion or inappropriate cell adhesion ( 8 ). (spandidos-publications.com)
- Increased Bim(EL) levels induce apoptosis in suspended cells and are required for anoikis in B-RAF-depleted cells. (nih.gov)
- In this study, we show that metformin can induce instability of ΔNp63α protein, leading to subsequent anoikis. (aacrjournals.org)
- Etoposide, adriamycin, vinblastine, cisplatin and paclitaxel were able to induce apoptosis in human osteosarcoma cells SAOS-2 regardless of their anoikis resistance phenotype or the culture conditions (adhered vs. suspended). (biomedcentral.com)
- Immunohistochemistry studies in melanoma indicate that up-regulation of Bcl- XL and Mcl-1 correlates with melanoma progression ( 13 ), but the role of Bcl-2 family proteins in resistance to melanoma anoikis remains unknown. (aacrjournals.org)
- While the precise role of anoikis resistance in osteosarcoma progression is still unclear, chemoresistance continues to be an important problem in the clinic. (biomedcentral.com)
- Therefore, understanding how normal HMECs overcome anoikis may provide insights into breast cancer initiation and progression. (beds.ac.uk)
Apoptosis that is induced1
- Anoikis is defined as apoptosis that is induced by inadequate or inappropriate cell-matrix interactions. (nih.gov)
- Oncogene-mediated resistance to anoikis has also been shown in other tumor cell types, for example, by overexpression of epidermal growth factor receptor in breast cancer cells ( 10 ). (aacrjournals.org)
- Finally, inhibition of epidermal growth factor receptor kinase activity did not overcome Ras inhibition of anoikis, indicating that this autocrine loop essential for transformation is not involved in anoikis protection. (asm.org)
- Monosaccharide digitoxin derivative sensitize human non-small cell lung cancer cells to anoikis through Mcl-1 proteasomal degradation. (cdc.gov)
- In addition, D6-MA also targeted Mcl-1 degradation causing an increased anoikis in A549 lung cancer cells. (cdc.gov)
- Molecular mechanisms that control anoikis of nonmalignant and cancer cells are understood poorly. (sigmaaldrich.com)
- In this study, we investigated the molecular mechanisms of a novel marine bacterial polysaccharide EPS11 which exerts its cytotoxic effects through affecting cancer cell adhesion and anoikis. (mdpi.com)
- Elevated PLK1 expression contributes to protection against anoikis in cancer cells through the regulation of β-catenin expression. (aacrjournals.org)
- Thus, elucidating the molecular mechanisms involved in cancer-associated anoikis resistance is critical for the development of therapies designed to restore the sensitivity of malignant cells to anoikis. (aacrjournals.org)
- 2014). 'Correlation between E-Cadherin-Regulated Cell Adhesion and Human Osteosarcoma MG-63 Cell Anoikis', Asian Pacific Journal of Cancer Prevention , 15(19), pp. 8203-8207. (waocp.org)
- Because anoikis deficiency is a key feature of neoplastic transformation and invasive growth of epithelial cancer cells, our study on the role of EMMPRIN in anoikis resistance and the mechanism involved underscores the potential of EMMPRIN expression as a prognostic marker and novel target for cancer therapy. (elsevier.com)
- TGF-beta has paradoxical and context dependent effects on proliferation and anoikis in human colorectal cancer cell lines. (nih.gov)
- We investigated the effect of TGF-beta on anoikis in colorectal cancer cell lines sensitive to TGF-beta-mediated growth inhibition to determine if the context of the cells could be one of the factors that would affect whether TGF-beta exerts tumor suppressor or oncogene activity on colon cancer cells. (nih.gov)
- Molecular mechanisms underlying resistance to anoikis have not been reported in thyroid cancer cells. (cdc.gov)
- Furthermore, inhibition of ILK activity induced anoikis in two anoikis-resistant human breast cancer cell lines. (nih.gov)
- Protein Kinase A Activation Promotes Cancer Cell Resistance to Glucose Starvation and Anoikis. (uni.lu)
- en] Cancer cells often rely on glycolysis to obtain energy and support anabolic growth. (uni.lu)
- Using omics and computational analyses, we found that cyclic adenosine monophosphate-Protein Kinase A (cAMP-PKA) axis activation is fundamental for cancer cell resistance to glucose starvation and anoikis. (uni.lu)
- Our results reveal for the first time the role of the versatile PKA in cancer cells survival under chronic glucose starvation and anoikis and may be a novel potential target for cancer treatment. (uni.lu)
- Since anoikis resistance plays a critical role in solid tumor growth, we investigated the relevance of these findings in the context of breast cancer. (beds.ac.uk)
- But in order for cancer cells to metastasize they have to leave their homes and to survive while traveling they must resist anoikis - like a third-grader at sleep-away camp. (redorbit.com)
- This most aggressive form of breast cancer didn't care - it had learned to be anoikis-resistant. (redorbit.com)
- Unbound cancer cells that are immune to anoikis are most dangerous - they can travel away from their home to invade other tissues. (redorbit.com)
- Unbound cancer cells sensitized to anoikis by the reintroduction of miR-200c aren't dangerous at all. (redorbit.com)
- Thus, we assessed the effect of TGF-β1 on anoikis in established colorectal human cancer cell lines. (vanderbilt.edu)
- Therefore, TGF-β paradoxically promotes the malignant behavior of a subset of TGF-β responsive colon cancer cell lines by blocking anoikis through cell-autonomous mechanisms. (vanderbilt.edu)
- To investigate the molecular mechanisms through which polo-like kinase-1 (PLK1) takes part in anoikis resistance of esophageal squamous cell carcinoma (ESCC) cells. (aacrjournals.org)
- Purpose: The aim of this study was to investigate the relationship between cell adhesion and anoikis evasionamong human osteosarcoma cells (MG-63), and to further study the molecular mechanisms. (waocp.org)
- Numerous apoptotic stimuli, including growth factor withdrawal, anoikis, and DNA damage, as well as cytotoxic compounds like staurosporine, result in Bax translocating to the OMM, where it assembles into high molecular weight complexes [ 8 - 10 ]. (pubmedcentralcanada.ca)
- Furthermore, these cells manifest increased sensitivity to anchorage deprivation-induced apoptosis (anoikis) ( 11 ). (pnas.org)
Known as anoikis2
- Dramatic changes of pressure in the local circulation flow field would lead to alterations in biorheological characteristics of Endothelial cells(ECs), and futher resulted in the apoptosis induced by loss of anchorage, a form of cell death known as anoikis. (scirp.org)
- Epithelial cells are homebodies - they like to attach to things and becoming detached initiates a form of cell suicide known as anoikis (literally "homeless" in Latin). (redorbit.com)
Inhibition of anoikis2
- Surprisingly, our analyses of Ras effector domain mutants or constitutively activated effectors indicated that activation of Raf-1, phosphatidylinositol 3-kinase (PI3K), or RalGDS alone is not sufficient to promote Ras inhibition of anoikis. (asm.org)
- Overexpression of ILK in the anoikis-sensitive SCP2 cells results in a profound inhibition of anoikis, as determined by annexin V binding and activation of caspases 8 and 3. (nih.gov)
Protection from anoikis2
- In melanoma, B-RAF-mediated protection from anoikis is mediated, at least in part, by the down-regulation of two BH3-only proteins, Bim EL and Bad ( 9 ). (aacrjournals.org)
- The presence of CTM supports the speculation that cells within CTM have a survival advantage via protection from anoikis (24-26). (thefreedictionary.com)
Cell death induced1
- A functional screening using this library led to the identification of hsa-miR-30b and hsa-miR-30c as negative regulators of cell death induced by loss of attachment (anoikis). (rug.nl)
- expression with lentiviral short hairpin RNA sensitized IEC-Ras to anoikis and decreased PC degradation, but did not change PC synthesis. (dal.ca)
- When cells are detached from the ECM, there is a loss of normal cell-matrix interactions, and they may undergo anoikis. (wikipedia.org)
- Many normal cell types, including epithelial cells, undergo apoptosis upon detachment from their proper substratum, a phenomenon termed anoikis ( 4 - 6 ). (aacrjournals.org)
- Loss of expression of tropomyosin-1, a novel class II tumor suppressor that induces anoikis , in primary breast tumors. (thefreedictionary.com)