• 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)
  • Anoikis is a specific type of apoptosis that plays a vital physiological role in regulating tissue homoeostasis. (spandidos-publications.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)
  • 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 is a specific type of apoptosis induced by loss of cell adhesion or inappropriate cell adhesion ( 8 ). (spandidos-publications.com)
  • Additionally, apoptosis/anoikis was induced by pharmacological inhibition of Fak (PF573228) or Src (PP2). (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)
  • Induces apoptosis and anoikis. (uniprot.org)
  • When deprived of anchorage, normal epithelial cells undergo detachment-induced apoptosis, or anoikis, irrespective of the presence of growth factors ( Gilmore, 2005 ). (rupress.org)
  • 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. (uniss.it)
  • Tissue inhibitor of metalloproteinase 1 expression associated with gene demethylation confers anoikis resistance in early phases of melanocyte malignant transformation. (thermofisher.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)
  • 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)
  • 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)
  • and cell-cell contact mediated resistance to anoikis implicates PI3K pathway in a highly relevant cell model (HEK293ar). (biomedcentral.com)
  • 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. (wiley.com)
  • 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)
  • Previous investigations have implied that activation or overexpression of TrkB promoted proliferation, survival, angiogenesis, anoikis-resistance and metastasis in human cancers. (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 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)
  • The inhibitor induces anoikis and blocks many functions important for ovarian cancer metastasis including, c-Met signaling, adhesion, invasion, and proliferation. (aacrjournals.org)
  • TGF-beta has paradoxical and context dependent effects on proliferation and anoikis in human colorectal cancer cell lines. (nih.gov)
  • Knockdown of endogenous cytoplasmic PTK6 in PC3 prostate cancer cells impairs proliferation, migration and anoikis resistance. (wiley.com)
  • 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)
  • Regulation of anoikis in human intestinal epithelial cells (IECs) implicates differentiation state-specific mechanisms. (biomedcentral.com)
  • Anoikis-resistance is of critical importance for metastasis of various human cancers including mRCC. (spandidos-publications.com)
  • Anoikis-resistance is consequently an essential prerequisite of progression and metastasis of various human cancer types ( 10 , 11 ). (spandidos-publications.com)
  • 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)
  • 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 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)
  • 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)
  • 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)
  • 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)
  • We report herein that differentiated IECs exhibit a greater sensitivity to anoikis than undifferentiated ones. (biomedcentral.com)
  • Knock-down of HAb18G/CD147 and E-cadherin inhibited cell-cell contacts formation and increased anoikis sensitivity respectively. (biomedcentral.com)
  • Failure of anoikis execution could result in adherent cells surviving under suspension conditions or at ectopic sites. (spandidos-publications.com)
  • The role of PLK1 in cell anoikis resistance was examined by ectopic gene expression and siRNA-mediated knockdown. (aacrjournals.org)
  • Nitric oxide mediated caveolin-1 upregulation, anoikis resistance and increase migration. (hindawi.com)
  • Upregulation of HAb18G/CD147 in suspended HEK293ar cells suppressed anoikis by mediating the formation of cell-cell adhesions. (biomedcentral.com)
  • Therefore, we addressed the function of HIF-1α in anoikis resistance and anchorage-independent growth. (aacrjournals.org)
  • Hence, our data argue for a pivotal role for HIF-1α in anoikis control via suppression of α5 integrin. (aacrjournals.org)
  • 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)
  • 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)
  • 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)
  • 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)
  • Elevated PLK1 expression contributes to protection against anoikis in cancer cells through the regulation of β-catenin expression. (aacrjournals.org)
  • PLK1 protects esophageal carcinoma cells from anoikis through modulation of β-catenin protein levels by inhibiting their degradation. (aacrjournals.org)
  • Taken together, this study reveals critical mechanisms involved in the role of RelA/PLK1/β-catenin in anoikis resistance of ESCC cells. (aacrjournals.org)
  • 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)
  • 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)
  • However, when tumour cells detach they resist anoikis, allowing them to migrate to new sites and seed new tumours. (oup.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)
  • Additionally, we show that α2β1 and α5β1 suppress anoikis in undifferentiated cells, whereas α3β1 does so in differentiated ones. (biomedcentral.com)
  • An anoikis-resistant clone (HEK293ar), derived from anoikis-sensitive parental Human Embryonic Kidney 293 cells, survived anoikis by the formation of cell-cell contacts. (biomedcentral.com)
  • Anoikis resistance in HEK293ar cells also required E-cadherin-mediated cell-cell contacts. (biomedcentral.com)
  • Furthermore, acquisition of anoikis resistance is required for cells used in engineering during adaptation to suspension culture and spheroid growth. (biomedcentral.com)
  • levels in FVSMC could represent and adaptive mechanism resulting in the anoikis resistance of these cells. (uniss.it)
  • Therefore, we investigated whether α2β1, α3β1, α5β1, and α6β4 integrins perform differentiation state-specific roles in the suppression of IEC anoikis. (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)
  • However, the precise mechanisms on anoikis-resistance in mRCC are still unclear. (spandidos-publications.com)
  • Anoikis-resistance is closely related to mRCC ( 12 , 13 ), while the exact mechanisms of anoikis-resistance in mRCC remain unclear. (spandidos-publications.com)
  • Electrophoretic mobility shift assay, chromatin immunoprecipitation, and reporter gene assays were carried out to identify the transcription factors responsible for PLK1 expression during anoikis resistance. (aacrjournals.org)
  • In this study, we show that metformin can induce instability of ΔNp63α protein, leading to subsequent anoikis. (aacrjournals.org)
  • We observed variable effects of TGF-beta on anoikis in these cell lines, even though they all are growth-inhibited by TGF-beta. (nih.gov)
  • The aim of the present study was to explore the impact of TrkB on anoikis-resistance and targeted therapy in mRCC. (spandidos-publications.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)
  • Normal cells undergo anoikis when they lose adhesion to or encounter an inappropriate extracellular matrix. (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)
  • Anoikis is a form of apoptosis induced by loss of adhesion or adhesion to an inappropriate extracellular matrix ( 1 ). (aacrjournals.org)
  • 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)
  • 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 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)
  • Another MEK inhibitor PD98059 also induced anoikis sensitivity in MDA-MB231 cells but not in HBC4 cells. (aacrjournals.org)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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 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)
  • 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)
  • 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)
  • 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)
  • Depletion of Bim together with Bad has an additive effect on protecting B-RAF knockdown cells from anoikis. (nih.gov)
  • 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)
  • 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)
  • 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)
  • We found that enforced downregulation of Chk2 protects intestinal epithelial cells from anoikis. (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)
  • 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 "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)
  • 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)
  • 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 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)
  • 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)
  • These results suggest that LMO3 promotes HCC cell invasion and anoikis inhibition by interacting with LATS1 and suppressing Hippo signaling. (springer.com)
  • In a 2004 publication, Higuchi and Jass (11) updated these concepts, stating: "Using more modern terminology, the hyperplastic polyp can be defined as a lesion caused by the inhibition of programmed cell death or apoptosis," which they explain is probably a special form of apoptosis called anoikis that is associated with programmed exfoliation of surface epithelial cells. (thefreedictionary.com)
  • 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)
  • 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)
  • Additionally, apoptosis/anoikis was induced by pharmacological inhibition of Fak (PF573228) or Src (PP2). (biomedcentral.com)
  • We show that restoration of miR-200c to ovarian cancer cells results in increased anoikis sensitivity and reduced adherence to biologic substrates in vitro . (aacrjournals.org)
  • Because both chemo- and anoikis-resistance are critical steps in the progression of ovarian cancer, we sought to determine how restoration of miR-200c affects tumor burden and chemosensitivity in an in vivo preclinical model of ovarian cancer. (aacrjournals.org)
  • However, the mechanisms underlying anoikis resistance in ovarian cancer are still unclear. (biomedcentral.com)
  • 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)
  • 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)
  • As an additional level of growth control, epithelial cells respond to loss of matrix adhesion by induction of programmed cell death (anoikis) even in the presence of growth factors that normally promote proliferation ( 16 ). (asm.org)
  • 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)
  • 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)
  • These data further the functional understanding of the concept that the suppression of anoikis is subjected to cell differentiation state-selective mechanisms. (biomedcentral.com)
  • 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)
  • 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)
  • Loss of expression of tropomyosin-1, a novel class II tumor suppressor that induces anoikis , in primary breast tumors. (thefreedictionary.com)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • en] Cancer cells often rely on glycolysis to obtain energy and support anabolic growth. (uni.lu)
  • In addition we identify also a PKA/Src mechanism capable to protect cancer cells from 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)
  • Therefore, understanding how normal HMECs overcome anoikis may provide insights into breast cancer initiation and progression. (beds.ac.uk)
  • 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)
  • 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)
  • By contrast, oncogenic signaling in tumor cells enables resistance to anoikis, a trait that contributes to tumor progression. (nih.gov)
  • 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)
  • However, when tumour cells detach they resist anoikis, allowing them to migrate to new sites and seed new tumours. (oup.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)
  • Additionally, we show that α2β1 and α5β1 suppress anoikis in undifferentiated cells, whereas α3β1 does so in differentiated ones. (biomedcentral.com)
  • 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)
  • 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)
  • Acquisition of anoikis resistance in human osteosarcoma cells does not result in a generalized resistance to all apoptotic stimuli, including chemotherapy. (biomedcentral.com)
  • By contrast, malignant cells display resistance to anoikis, a trait that permits their survival at sites distant from the primary tumor. (aacrjournals.org)
  • Anoikis resistant tumor cells have circumvented the death signals generated by the lack of attachment affording them increased survival times while migrating to secondary sites. (biomedcentral.com)
  • GSE treatment of cells led to their detachment within 12 hours, as occurs in anoikis, and caused a significant decrease in live cells mostly due to their apoptotic death. (aacrjournals.org)
  • DSF/Cu induced anoikis and significantly suppressed cell migration and invasion with negative effects on focal adhesions, coinciding with vimentin breakdown and calpain activation in TNBC cells. (elsevier.com)
  • In vitro transwell matrigel invasion assay and annexin V anoikis assay in HCC cells were conducted to investigate LMO3 related biological functions. (springer.com)
  • 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)
  • Finally, we show that Wnt11 promotes activation of RhoA, which causes ILC anoikis resistance. (biologists.org)
  • ATF4 confers resistance to anoikis. (jci.org)