• This gene encodes the cyclin-dependent kinase inhibitor p21(WAF1/Cip1), a factor implicated in cell cycle, senescence, and cancer. (ed.ac.uk)
  • This new and unprecedented evidence for a link between SdhD dysfunction and p21(WAF1/Cip1) will open new avenues for the study of the mechanisms that cause tumors in Sdh mutants. (ed.ac.uk)
  • Primary mouse embryo fibroblasts lacking Cip1 and Kip1 genes encoding inhibitors of cyclin-dependent kinase-2 were used to further explore the effects of oncogenic Ras on arrest of the cell division cycle. (ku.dk)
  • Although early passage primary fibroblast strains that lack both p21(Cip1) and p27(Kip1) fail to assemble cyclin D-dependent kinases, oncogenic Ras retained its ability to induce p19(ARF), but not p16(INK4a), protecting Cip/Kip-null cells from proliferating and undergoing transformation. (ku.dk)
  • Therefore, in the absence of p16(INK4a), p21(Cip1), and p27(Kip1), oncogenic Ras affects the functions of genes required for completion of the cell cycle. (ku.dk)
  • In this model, CDK4 overexpression results in increased CDK2 activity associated with the noncatalytic function of CDK4, sequestration of p21(Cip1) and p27(Kip1). (duke.edu)
  • We observed elevated levels of p21(Cip1) in K5Cdk2, but not in K5Cdk4(D158N), epidermis, suggesting that CDK2 overexpression elicits a p21(Cip1) response to maintain keratinocyte homeostasis. (duke.edu)
  • TGF-b inhibits cell growth by controlling a cytostatic program that includes activation of the cyclin-dependent kinase inhibitors p15 Ink4B and p21 WAF1/Cip1 and repression of c-myc. (tmc.edu)
  • Specifically, DLX4 blocked the ability of TGF-b to induce expression of p15 Ink4B and p21 WAF1/Cip1 by directly binding to Smad4 and to Sp1. (tmc.edu)
  • In addition, DLX4 induced expression of c-myc, a repressor of p15 Ink4B and p21 WAF1/Cip1 transcription, independently of TGF-b signaling. (tmc.edu)
  • Cell cycle progression is faster in cells in which invadopodia are abolished (by Tks5 knockdown), evidenced by earlier induction of cyclins A and B. A close look at the regulators of G1 revealed that the overexpression of p27 kip1 , but not p21 cip1 , causes faster turnover of invadopodia and increased ECM degradation. (biorxiv.org)
  • In recent years, cell cycle regulators have been shown to exhibit roles in both tumor suppression and tumor promotion, particularly cyclin-dependent kinase inhibitors (CKI) p27 kip1 and p21 cip1 14 . (biorxiv.org)
  • We demonstrated that deferasirox increased expression of the metastasis suppressor protein N-myc downstream-regulated gene 1 and upregulated the cyclin-dependent kinase inhibitor p21(CIP1/WAF1) while decreasing cyclin D1 levels. (birmingham.ac.uk)
  • Subcellular localisation of cyclin B, Cdc2 and p21(WAF1/CIP1) in breast cancer. (ox.ac.uk)
  • The heterodimeric cyclin B/Cdc2 protein kinase governs entry into mitosis, and can be negatively regulated through p53-mediated transcriptional induction of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1). (ox.ac.uk)
  • Ectopic expression of p21(WAF1/CIP1) in cultured cells has been shown previously to influence the subcellular distribution of the cyclin-dependent kinases (CDKs) including Cdc2. (ox.ac.uk)
  • In this study, we have examined the subcellular localisation of Cdc2, cyclin B and p21(WAF1/CIP1) by immunohistochemistry in a well characterised series of primary breast cancers. (ox.ac.uk)
  • cytoplasmic p21(WAF1/CIP1) and high cyclin B levels were also significant predictors of poor prognosis. (ox.ac.uk)
  • Investigation of the subcellular distribution of cell cycle regulatory proteins, particularly p21(WAF1/CIP1), could provide valuable prognostic markers in breast cancer. (ox.ac.uk)
  • Although carcinogenic roles for the INK4B, INK4C, INK4D, CIP1, KIP1, and KIP2 genes appear to be limited, INK4A is among the most commonly mutated genes in human tumors. (medscape.com)
  • DNA demethylation, as well as methylation, of certain genes allows for neurogenesis to proceed in a time dependent manner. (wikipedia.org)
  • succinate dehydrogenase, Sdh) genes cause familiar pheochromocytoma/paraganglioma tumors. (ed.ac.uk)
  • One of the activated genes is an inhibitor of cyclin-dependent kinases. (lsbio.com)
  • Since the recruitment of HDAC leads to transcriptional repression, inhibitors of this enzymatic activity can reverse aberrant repression in cancer cells and lead to re-expression of epigenetically silenced genes involved in growth and differentiation processes. (iiarjournals.org)
  • Importantly, in the cohort studied, Ser312 mutation predisposes mice to develop thymic lymphomas and liver tumors, partly due to p53Ser312Ala's inability to fully induce a set of p53 target genes including p21 and cyclin G1. (ox.ac.uk)
  • Driver events in pediatric malignancies can occur through loss of function in tumor suppressor genes or gain of function in proto-oncogenes. (medscape.com)
  • Tumor suppressor genes encode proteins that normally provide negative control of cell proliferation. (medscape.com)
  • Genes necessary for cell cycle progression, such as E2F-dependent genes, are incorporated into the SAHF and are thereby silenced, contributing to the stability of the growth arrest. (rupress.org)
  • These events are dependent on the proper levels of transcription and translation of certain genes. (cancerquest.org)
  • This first category also includes genes that contribute to tumor growth by inhibiting cell death. (cancerquest.org)
  • The genes in the second group are called tumor suppressors. (cancerquest.org)
  • This is in contrast with tumor suppressor genes which must BOTH be defective to lead to abnormal cell division. (cancerquest.org)
  • It is postulated to bind as a tetramer to a p53-binding site and activate expression of downstream genes that inhibit growth and/or invasion, and thus function as a tumor suppressor. (affbiotech.cn)
  • In addition, these alterations affect 3 principal categories of genes, as follows: proto-oncogenes, tumor suppressor genes, and DNA repair genes. (medscape.com)
  • This article briefly discusses tumor suppressor genes and then focuses on the role of proto-oncogenes in childhood cancer. (medscape.com)
  • Inactivation of tumor suppressor genes, whose products normally provide negative control of cell proliferation, contributes to malignant transformation in various cell types. (medscape.com)
  • Like Rb protein, many of the proteins encoded by tumor suppressor genes act at specific points in the cell cycle. (medscape.com)
  • TP53 activates the expression of genes involved in apoptosis, cell cycle regulation (p21), and MDM2. (medscape.com)
  • Another important class of tumor suppressor genes involved in cell cycle control and in the generation of human cancers is the cyclin-dependent kinase (CDK) inhibitors. (medscape.com)
  • In response to DNA-damaging agents, the wild-type p53-activated fragment 1 (WAF1 also known as p21) is an important downstream effector in the p53-specific growth arrest pathway. (lu.se)
  • Similarly, depletion in the STRIPAK component STRIP1 affects activation of GCKIII kinases and cell cycle disruption through elevated expression of cyclin dependent kinase inhibitors p21 and p27, enhanced levels of which lead to a protective effect from therapeutic treatments and increased proliferation. (lu.se)
  • It affects cell proliferation, differentiation and inhibits apoptosis, and its role in tumor development has received attention ( 9 ). (spandidos-publications.com)
  • Overexpression of IGF-1 in serum and tissue alters the growth of normal cells and causes uncontrolled proliferation, inhibits differentiation and reduces apoptosis, resulting in the incidence and development of malignant tumors ( 10 ). (spandidos-publications.com)
  • Hematopoietic progenitor kinase 1 (HPK1) regulates stress responses, proliferation, and apoptosis in hematopoietic cells. (aacrjournals.org)
  • Although the senescent cells remain viable, they show typical changes with enlarged and flattened cell bodies, apoptosis resistance, increased activity of senescence-associated β -galactosidase (SA- β -gal), and upregulation of cyclin-dependent kinase (CDK) inhibitors including p16 INK4A , ARF proteins, and p21 [ 13 - 16 ]. (hindawi.com)
  • LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seem to have to effect on cell-cycle regulation. (lsbio.com)
  • Upon treatment with Plk1 inhibitors, p53 in tumor cells is activated and induces strong apoptosis, whereas tumor cells with inactive p53 arrest in mitosis with DNA damage. (oncotarget.com)
  • In addition, compared to the mono-treatment, combination of Polo-like kinase 1 inhibition with anti-mitotic or DNA damaging agents boosts more severe mitotic defects, effectually triggers apoptosis and strongly inhibits proliferation of cancer cells with functional p53. (oncotarget.com)
  • It was identified that propofol inhibited the viability and invasion, but promoted apoptosis of HGC‑27 and AGS cells in a dose‑dependent manner. (spandidos-publications.com)
  • Vinca alkaloids are also thought to increase apoptosis by increasing concentrations of p53 (cellular tumor antigen p53) and p21 (cyclin-dependent kinase inhibitor 1) and by inhibiting Bcl-2 activity. (smpdb.ca)
  • Dormancy can be induced by more than one mechanism: cellular dormancy (quiescence), angiogenic dormancy (tumor mass size limit), and immunologic dormancy (immunosurveillance, balance between proliferation and apoptosis). (biomedcentral.com)
  • Cyclin-dependent kinase inhibitors (CDKIs) are proteins that bind to and inhibit the activity of CDKs. (prospecbio.com)
  • Cyclins regulate the cell cycle in association with cyclin dependent kinases (CDKs). (biomedcentral.com)
  • CDKs are under inhibitory control of cyclin dependent kinase inhibitors (CDKIs). (biomedcentral.com)
  • The progression of cells through the cell cycle is regulated by a family of protein kinases known as the cyclin-dependent kinases (CDKs). (biomedcentral.com)
  • Cyclins function as the positive regulators of CDKs. (biomedcentral.com)
  • D-type and E-type cyclins assemble with CDKs during the G1 phase and these holoenzymes act as rate-limiting controllers to regulate passage through the restriction point and the subsequent onset of DNA replication [ 2 , 3 ]. (biomedcentral.com)
  • Cyclins and CDKs assemble into complexes with one another as cells progress through G1 phase, cyclins being required to activate the serine-threonine kinase activity of their catalytic partners. (biomedcentral.com)
  • Furthermore, CDK-activating kinase (CAK) phosphorylates cyclin-bound CDKs on a single threonine residue, a modification that is essential for their activity [ 6 - 9 ]. (biomedcentral.com)
  • The p27 protein is a canonical negative regulator of cell proliferation and acts primarily by inhibiting cyclin-dependent kinases (CDKs). (rcsb.org)
  • The cyclin-dependent kinase (CDK) inhibitors p21 and p16 inhibit the activity of CDKs, such as CDK4. (medscape.com)
  • In addition, numerous important cellular proteins, such as B-cell lymphoma-2 homologous antagonist/killer, Myc proto-oncogene protein, cyclin-dependent kinase inhibitor 1B, DNA replication licensing factor MCM-7, retinoblastoma 1 and Annexin A1, are degenerated through the UBE3A-mediated ubiquitin proteasome pathway ( 7 ). (spandidos-publications.com)
  • CDKIs are capable of suppressing growth, and several lines of evidence strongly suggest that at least some CDKIs may be tumor suppressor proteins. (prospecbio.com)
  • Two powerful tumour suppressor pathways, controlled by the p53 and retinoblastoma (pRB) proteins, are important for establishing and maintaining the senescence growth arrest. (nature.com)
  • We will discuss three key proteins that function as tumor suppressors implicated in the development of pediatric (and some adult) cancers: pRB, p53, and PTEN. (medscape.com)
  • The D158N mutation blocks CDK4 kinase activity without interfering with its binding capability. (duke.edu)
  • We found that p27, when phosphorylated by tyrosine kinases, allosterically activated CDK4 in complex with cyclin D1 (CDK4-CycD1). (rcsb.org)
  • Structural and biochemical data revealed that binding of phosphorylated p27 (phosp27) to CDK4 altered the kinase adenosine triphosphate site to promote phosphorylation of the retinoblastoma tumor suppressor protein (Rb) and other substrates. (rcsb.org)
  • Palbociclib instead primarily targeted monomeric CDK4 and CDK6 (CDK4/6) in breast tumor cells. (rcsb.org)
  • Our data characterize phosp27-CDK4-CycD1 as an active Rb kinase that is refractory to clinically relevant CDK4/6 inhibitors. (rcsb.org)
  • ST caused G0/G1 cell cycle arrest which was accompanied by a decrease in CDK4 and cyclin D1, and an increase in p21/Cip1and p27/Kip1 protein levels. (biomedcentral.com)
  • The p16INK4A protein is a cell-cycle inhibitor that acts by inhibiting activated cyclin D:CDK4/6 complexes, which play a crucial role in the control of the cell cycle by phosphorylating Rb protein. (medscape.com)
  • Estrogen receptor-alpha (ERalpha) promotes proliferation of breast cancer cells, whereas tumor suppressor protein p53 impedes proliferation of cells with genomic damage. (nih.gov)
  • Ionizing radiation together with ERalpha knock down results in additive effect on transcription of endogenous p53-target gene p21 (CDKN1) in human breast cancer cells. (nih.gov)
  • The overexpression of miRNA‑375 significantly increased caspase‑3 and caspase‑9 activities, induced B‑cell lymphoma 2 (Bcl‑2)/Bcl‑2‑associated X protein, tumor protein 53 and cyclin‑dependent kinase inhibitor 1 protein expression and suppressed cyclin D1 and survivin protein expression in HPV‑18(+) cervical cancer cells. (spandidos-publications.com)
  • Previous studies have identified that UBE3A exhibits abnormal expression in numerous tumor cells, including prostate, cervical and breast cancer ( 6 , 7 ). (spandidos-publications.com)
  • ILC-LTED cells remained dependent on WNT4 for proliferation, by either maintaining ER function and WNT4 regulation or uncoupling WNT4 from ER and upregulating WNT4 expression. (nih.gov)
  • In ILC and ILC-LTED cells, WNT4 led to suppression of CDKN1A/p21, which is critical for ILC cell proliferation. (nih.gov)
  • Increasing evidence indicates that senescent cells could be a promising new target for therapeutic intervention known as senotherapy, which includes depleting senescent cells, modulating SASP and restoration of senescence inhibitors. (frontiersin.org)
  • Treatment of Panc-1 cells with a proteasome inhibitor, MG132, increased the HPK1 protein levels in a dose-dependent manner, suggesting that alteration in proteasome activity contributes to the loss of HPK1 protein expression in pancreatic cancer. (aacrjournals.org)
  • Like the endogenous HPK1, both wild-type HPK1 and its kinase-dead mutant, HPK1-M46, overexpressed in Panc-1 cells, were also targeted by proteasome-mediated degradation. (aacrjournals.org)
  • Furthermore, restoring wild-type HPK1 protein in PDA cells led to the increase in p21 and p27 protein expression and cell cycle arrest. (aacrjournals.org)
  • It turned out that old cells, on the one hand, act as tumor suppressors (since they irreversibly stop dividing themselves and reduce the risk of transformation of surrounding cells), and on the other hand, the specific metabolism of old cells can cause inflammation and degeneration of neighboring precancerous cells into malignant ones. (vechnayamolodost.ru)
  • They further link to the activation of protein kinase C- (PKC-) induced generation of reactive oxygen species (ROS) [ 6 , 7 ], which further mediates the activation of downstream transcription factor nuclear factor kappa-light-chain enhancer of activated B cells (NF- κ B). Thus, the main treatments of DN refer to modulate glycemic and blood pressure through insulin and RAS inhibitors. (hindawi.com)
  • Furthermore, senescent cells, with the secretory features known as the senescence-associated secretory phenotype (SASP), could produce proinflammatory cytokines, such as tumor necrosis factor- α (TNF- α ), interleukin-6 (IL-6), and monocyte chemoattractant protein1 (MCP-1), to greatly affect the neighboring cells [ 17 , 18 ]. (hindawi.com)
  • En face co-immunostaining of the mouse aortic arch revealed a low level of PDCD4 in endothelial cells undergoing pulsatile shear stress. (plos.org)
  • In contrast to normal cells, many tumors are resistant to the anti-proliferative effect of TGF-b. (tmc.edu)
  • p27 is a cyclin-dependent kinase inhibitor with many putative functions in normal and neoplastic cells. (umich.edu)
  • Polyvinyl pyrrolidone-coated silver nanoparticles in a human lung cancer cells: time- and dose-dependent influence over p53 and caspase-3 protein expression and epigenetic effects. (sciendo.com)
  • Expression of p15, p16, p21 and p27 did not vary in granulosa and theca cells by the follicle stage. (biomedcentral.com)
  • D-type cyclins are usually synthesized by mid-G1 phase and accumulate to a maximum as cells advance through the G1/S boundary. (biomedcentral.com)
  • p53 represses the promoter of Polo-like kinase 1, whereas Polo-like kinase 1 inhibits p53 and its family members p63 and p73 in cancer cells lacking functional p53. (oncotarget.com)
  • Plk1 inhibitors target all rapidly dividing cells irrespective of tumor cells or non-transformed normal but proliferating cells. (oncotarget.com)
  • Thus, inactive p53 is not associated with a susceptible cytotoxicity of Polo-like kinase 1 inhibition and could rather foster the induction of polyploidy/aneuploidy in surviving cells. (oncotarget.com)
  • In this regard, restoration of p53 in tumor cells with loss or mutation of p53 will reinforce the cytotoxicity of combined Polo-like kinase 1 therapy and provide a proficient strategy for combating relapse and metastasis of cancer. (oncotarget.com)
  • Tumor cell invasion and metastasis require cancer cells to be both proliferative and invasive, i.e. migrate through the tissue and assemble invadopodia. (biorxiv.org)
  • Metastasis is a complex, multi-step process that is initiated when cancer cells in the primary tumor acquire invasive properties, including motility and the ability to breakdown the extracellular matrix (ECM) 1 , and is responsible for the majority of cancer-related mortalities 2 . (biorxiv.org)
  • However, under these microenvironmental conditions, only 15% of tumor cells assemble invadopodia at any given time, while the rest are non-motile. (biorxiv.org)
  • Propofol could inhibit Bcl‑2 and MMP9 expression, and increase P21 expression in GC cells. (spandidos-publications.com)
  • Additionally, the effects of transfection with circ‑PVT1 small interfering RNA (si‑circ‑PVT1) on HGC‑27 and AGS cells could be reversed by treatment with miR‑195‑5p inhibitor. (spandidos-publications.com)
  • Previous studies have investigated the inhibitory effect of propofol on cancer cells in a variety of tumors, such as breast ( 2 ), lung ( 3 ) pancreatic ( 4 ), ovarian ( 5 ), hepatic ( 6 ) and gastric cancer (GC) ( 7 , 8 ). (spandidos-publications.com)
  • In GC, Yang et al ( 7 ) reported that propofol suppressed the proliferation of SGC-7901 and MGC-803 cells by promoting inhibitor of growth 3 ( 7 ). (spandidos-publications.com)
  • In this study, the anticancer properties of VPA on neural crest-derived human tumor cell lines G361 melanoma, U87MG glioblastoma and SKNMC Askin tumor cells were investigated. (iiarjournals.org)
  • We demonstrated previously that valproic acid (VPA) and other short-chain fatty acids, as HDAC inhibitors, can arrest cell growth and induce differentiation in human neuroblastoma cells ( 10 ). (iiarjournals.org)
  • The effectiveness of HDAC inhibitors, expecially VPA, in neuroblastoma cells, prompted us to investigate the anticancer activity of VPA in other neural crest-derived malignancies, such as glioblastoma, melanoma and Askin tumor. (iiarjournals.org)
  • In this study, we investigated the effect of VPA on cell proliferation, apoptotic activity and invasive ability in glioblastoma (U87MG), melanoma (G361) and Askin (SKNMC) tumor cells. (iiarjournals.org)
  • U87MG human glioblastoma and G361 human melanoma cells, obtained from Interlab Cell Line Collection (Genoa, Italy), and SKNMC Askin tumor cells, purchased from the American Type Culture Collection (Rockville, USA) were maintained in RPMI (Sigma, USA), supplemented with 10% fetal bovine serum (FBS), 2 mM glutamine, 50 U/ml penicillin and 50 μg/ml streptomycin and grown at 37°C in a humidified air with 5% CO 2 . (iiarjournals.org)
  • In this investigation, we examined the in vitro and in vivo activity of deferasirox against cells from human solid tumors. (birmingham.ac.uk)
  • The tumour microenvironment (TME) contains several other cell types apart from cancer cells which play a role not only in the regulation of the environment but in response to treatments. (lu.se)
  • Unlike their wild-type counterparts, human and mouse cells lacking p53 or p21 progress into mitosis prematurely with persisting uncapped telomeres. (ox.ac.uk)
  • Understanding the dormant stage of tumor cells may help in discovering ways to maintain the dormant state or permanently eliminate dormant residual disseminated tumor cells. (biomedcentral.com)
  • Tumor dormancy is a recognized clinical phenomenon in which disseminated tumor cells (DTCs) remain occult, asymptomatic, and undetectable over a prolonged period of time. (biomedcentral.com)
  • Dormancy can occur at the earliest stage of tumor development but also when remnant tumor cells escape treatment. (biomedcentral.com)
  • A tumor microenvironment that is altered (such as by frontline treatment) can mediate tumor cell entrance into, maintenance, and exit from dormancy through interaction with cells at niches, such as endothelial cells, stroma, or immune cells. (biomedcentral.com)
  • In MDA-MB-231 cells, ST caused a significant dose-dependent cell growth inhibition by 31- 63% (p ≤ 0.0001) in 48 h and 40-50% (p ≤ 0.0001) in 72 h. (biomedcentral.com)
  • In previous research, Kaempferia galanga L. extract - or KGE - demonstrated anti-cancer effects against Ehrlich ascites tumor cells (EATCs) in mice. (technologynetworks.com)
  • These changes can be inherited and are, therefore, found in every cell, but more often, they are somatically acquired and restricted to tumor cells. (medscape.com)
  • High tumor proliferation has previously been associated with response to chemotherapy. (lu.se)
  • Scholars@Duke publication: CDK2 activation in mouse epidermis induces keratinocyte proliferation but does not affect skin tumor development. (duke.edu)
  • We further demonstrated that overexpression of miR-24 suppressed the NPC cell proliferation and migration in vitro, and inhibited the xenograft tumor growth and lung metastasis in vivo. (biomedcentral.com)
  • PTEN encodes a protein kinase of the same name and functions as a tumor suppressor through regulation of cell proliferation. (medscape.com)
  • Three molecular mechanisms involved in tumor dormancy have been identified: cellular dormancy (quiescence or mitotic arrest), angiogenic dormancy (limited tumor size), and immunologic dormancy (immunosurveillance, balance between clearance and proliferation) (Figure 1 ). (biomedcentral.com)
  • 2017. Divergent roles of p120-catenin isoforms linked to altered cell viability, proliferation, and invasiveness in carcinogen-induced rat skin tumors. . (oregonstate.edu)
  • We also aimed to evaluate the expression of TGF-β1 and p27 in the context of other cell cycle and proliferation markers such as cyclin D1 and Ki-67. (biomedcentral.com)
  • Growth factors do not only stimulate cell proliferation, but they may also act as growth inhibitors, depending on the cell type and the stimulatory pathway that is involved. (biomedcentral.com)
  • Quantitative RT-PCR, MTT, colony formation, soft-agar, wound healing, Transwell migration and invasion assays, and xenograft tumor growth and lung metastasis models were performed to test the expression levels and functions of miR-24 in NPC. (biomedcentral.com)
  • Tumor dormancy can lead to tumor recurrence locally or to metastasis at a distant site. (biomedcentral.com)
  • While at Hopkins his work on the role of cell surface glycosylation in tumor metastasis led to a subsequent staff position at the NIH (National Institute on Aging) where he focused on tumor angiogenesis. (umaryland.edu)
  • Our findings suggest that in pancreatic carcinoma, TGF-β1 expression is related to tumor growth and metastasis. (biomedcentral.com)
  • In several types of tumors, particularly those of gastrointestinal origin, resistance to the anti-proliferative effect of TGF-b has been attributed to TGF-b receptor or Smad mutations. (tmc.edu)
  • However, these mutations are absent from many other types of tumors that are resistant to TGF-b-mediated growth inhibition. (tmc.edu)
  • To date, there have been no studies to investigate the effect of deferasirox on these types of tumors in vivo. (birmingham.ac.uk)
  • lt;div class="textblock">Oncogenic Ras induces two products of the INK4a/ARF tumor suppressor locus (p16(INK4a) and p19(ARF)) in primary human and rodent fibroblasts, ultimately leading to a permanent state of cell cycle arrest resembling replicative senescence. (ku.dk)
  • Whereas p16(INK4a) antagonizes the activities of cyclin D-dependent kinases, p19(ARF) activates the p53 transcription factor. (ku.dk)
  • The defining characteristic of senescence is a highly stable cell cycle arrest, triggered by the up-regulation of cyclin-dependent kinase inhibitors such as p16 INK4a and p21 CIP1a . (rupress.org)
  • Tumors that developed in mice deficient in INK4A were enhanced by the topical application of carcinogens and ultraviolet light. (medscape.com)
  • [ 5 ] Targeted disruption of TP53 in the mouse leads to the development of various tumors. (medscape.com)
  • DNA damage increases TP53 levels through an ATM-dependent pathway. (medscape.com)
  • In order to protect against itself, special cellular mechanisms of tumor suppression have formed in the body. (vechnayamolodost.ru)
  • Sager, R. Senescence as a mode of tumor suppression. (nature.com)
  • Phosphorylation of Ser312 contributes to tumor suppression by p53 in vivo. (ox.ac.uk)
  • p53, mdm-2, p21, and mib-1 expression were not significantly associated with response to chemotherapy, time to progression, or overall survival in the whole patient population or in the docetaxel group. (lu.se)
  • Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. (lsbio.com)
  • Although PDCD4 in general suppresses the development and progression of tumors, its specific biological functions differ by cell type [8] . (plos.org)
  • Deletion or mutation of the p16 gene leads to tumor development or tumor progression. (umich.edu)
  • Cell cycle progression is governed by a complex network of cyclin-dependent kinases that define not only the phase of the cell cycle, but also the timing of transitions between phases 13 . (biorxiv.org)
  • Overall, miR-24 acts as a novel tumor suppressor in the development and progression of NPC through targeting FSCN1 , which providing new insight into the mechanisms of NPC carcinogenesis and suggesting the possibility of miR-24 as a therapeutic target. (biomedcentral.com)
  • These results suggest that a p53-dependent pathway monitors telomere capping after DNA replication and delays G2/M progression in the presence of unprotected telomeres. (ox.ac.uk)
  • Tumor dormancy may contribute to tumor progression and relapse, either locally or metastatically at distant sites, years or decades after treatment. (biomedcentral.com)
  • To investigate this hypothesis, we generated two transgenic mouse models of elevated CDK2 kinase activity, K5Cdk2 and K5Cdk4(D158N) mice. (duke.edu)
  • In this study, we investigated whether DIM could improve insulin-dependent diabetes and nephropathy in streptozotocin (STZ)-induced diabetic mice. (researchgate.net)
  • It is a key effector of cellular senescence downstream of the tumor suppressor p53. (umich.edu)
  • Campisi, J. Cellular senescence as a tumor-suppressor mechanism. (nature.com)
  • Over the past decade, numerous studies indicate that various mechanisms of tumor dormancy exist, including cellular dormancy (quiescence), angiogenic dormancy, and immunologic dormancy. (biomedcentral.com)
  • Increasing evidence indicates that the dysregulation of miRNAs expression is involved in the tumorigenesis by acting as tumor suppressors or oncogenes. (biomedcentral.com)
  • The two-hit hypothesis has now been adopted as a key mechanism for the loss of function of tumor suppressors leading to oncogenesis. (medscape.com)
  • A useful analogy to consider when thinking about tumor suppressors and oncogenes is an automobile. (cancerquest.org)
  • Surprisingly, we found that neither CDK2 overexpression nor the indirect activation of CDK2 enhanced skin tumor development. (duke.edu)
  • 2011. NADPH oxidase overexpression in human colon cancers and rat colon tumors induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). . (oregonstate.edu)
  • The p21 family (p21, p27, p28 and p57) can bind to broad range of CDK-cyclin complexes and inhibit their activities. (prospecbio.com)
  • Cyclin E forms complexes during this interval with CDK2. (biomedcentral.com)
  • Polo-like kinase 1, a pivotal regulator of mitosis and cytokinesis, is highly expressed in a broad spectrum of tumors and its expression correlates often with poor prognosis, suggesting its potential as a therapeutic target. (oncotarget.com)
  • The extremely poor prognosis of patients affected by these highly chemoresistant tumors has not significantly improved in recent decades, therefore new approaches in therapeutic regimens are mandatory. (iiarjournals.org)
  • Pancreatic cancer is a malignant tumor with an extremely poor prognosis. (biomedcentral.com)
  • PCNA is a co-factor of cyclin-D and it makes a complex with cyclin-D, a cyclin dependent kinase (CDK), and a cyclin dependent kinase inhibitor (CDKI). (biomedcentral.com)
  • It has also been demonstrated that TGF-β induced cell cycle arrest can be partially attributed to the regulatory effects of TGF-β on both the expression and activity of cyclin-dependent kinase inhibitors [CDKI] such as p21 and p27. (biomedcentral.com)
  • Programmed cell death 4 (PDCD4) is an important tumor suppressor in the development of various human cancers [1] and inhibits translation rather than transcription. (plos.org)
  • p16 is a cyclin-dependent kinase inhibitor that has shown prognostic utility in some human cancers. (umich.edu)
  • Mutants of p53 that frequently occur in a number of different human cancers fail to bind the consensus DNA binding site, and hence cause the loss of tumor suppressor activity. (affbiotech.cn)
  • CircRNA-PVT1 (circ-PVT1) has been reported to function as an oncogenic circRNA in tumors, such as oral squamous cell carcinoma, head and neck squamous cell carcinoma, and osteosarcoma ( 13 - 15 ). (spandidos-publications.com)
  • Thus, HPK1 may function as a novel tumor suppressor and its loss plays a critical role in pancreatic cancer. (aacrjournals.org)
  • p53, the guardian of the genome, is the most important tumor suppressor. (oncotarget.com)
  • The meeting was attended by ∼70 investigators and included formal presentations, panel group discussions, and two breakout sessions that addressed targeted therapies in hematologic and solid tumors. (aacrjournals.org)
  • Collectively, we demonstrate that deferasirox is an orally effective antitumor agent against solid tumors. (birmingham.ac.uk)
  • It has been widely assumed that elevated CDK2 kinase activity plays a contributory role in tumorigenesis. (duke.edu)
  • Within the tumor microenvironment in vivo , invadopodia assembly is stimulated in areas rich in large blood vessels, macrophages and highly cross-linked ECM 11 . (biorxiv.org)
  • Perturbing any of these parameters has a direct effect on invadopodia function, establishing a strong in vivo correlation between the tumor microenvironment and invadopodia-driven motility. (biorxiv.org)
  • In this short review, we summarize recent experimental and clinical evidence for these three mechanisms and other possible tumor microenvironment mechanisms that may influence tumor dormancy. (biomedcentral.com)
  • [ 1 ] His prediction was subsequently supported by the cloning of the retinoblastoma tumor suppressor gene ( RB1 ) and by functional studies of the retinoblastoma protein, Rb. (medscape.com)
  • Furthermore, this study also provides insights into how aberrant activation of a developmental patterning gene promotes tumor pathogenesis. (tmc.edu)
  • Activation of p21 or p16 therefore causes cell cycle arrest. (medscape.com)
  • Thus, we demonstrate that phosphorylation of Ser312 is required for p53 to function fully as a tumor suppressor in vivo. (ox.ac.uk)
  • But at the same time, renewing tissues are subject to hyperproliferation, which leads to the formation of tumors, including malignant ones. (vechnayamolodost.ru)
  • In this work, we made use of the inducible SDHD-ESR mouse, a conditional mutant in the SdhD gene, which encodes the small subunit of MCII, and that acts as a tumor suppressor gene in humans. (ed.ac.uk)
  • RB1 encodes the protein pRB and was the first tumor suppressor gene to be molecularly defined. (medscape.com)
  • The analysis of the Hif1α pathway in SDHD-ESR tissues and in two newly derived cell lines after complete SdhD loss -a requirement for hereditary paraganglioma type-1 tumor formation in humans- partially recapitulated the "pseudo-hypoxic" response and rendered inconsistent results. (ed.ac.uk)
  • Five members of the Plk family have been discovered in humans and these serine/threonine kinases have emerged as key players by performing crucial functions in the cell cycle, DNA damage response and neuron biology [ 2 - 6 ]. (oncotarget.com)
  • However, many patients who exhibit no clinical symptoms after frontline therapy subsequently suffer, often many years later, aggressive tumor recurrence. (biomedcentral.com)
  • Tumor cell dormancy may help to explain treatment resistance and recurrence or metastatic reactivation. (biomedcentral.com)
  • Our recent report indicated that tumor suppressor gene ( p53 ) mutations and protein aberrant expression were detected in pterygium. (molvis.org)
  • Herpes virus thymidine kinase (HSV-tk) is used in suicide gene therapy. (umich.edu)
  • Western blotting was performed to detect the protein levels of cyclin‑dependent kinase inhibitor P21 (P21), B‑cell lymphoma‑2 (Bcl‑2), matrix metalloproteinase 9 (MMP9) and E26 oncogene homolog 1 (ETS1). (spandidos-publications.com)
  • In mouse embryonic stem cell-derived neural progenitors, increased histone acetylation induced by the histone deacetylase (HDAC) inhibitor valproic acid not only induced neuronal differentiation, but also selectively enriched the upper layer neuronal population. (wikipedia.org)
  • Recently, VPA has demonstrated antitumor activity as a histone deacetylase (HDAC) inhibitor. (iiarjournals.org)
  • Oncogenic Ras induces p19ARF and growth arrest in mouse embryo fibroblasts lacking p21Cip1 and p27Kip1 without activating cyclin D-dependent kinases. (ku.dk)
  • Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. (lsbio.com)
  • Therefore, detecting the expression of IGF-1 assists in determining the biological behavior of tumors ( 10 ). (spandidos-publications.com)
  • Although highly preliminary, the findings suggest that different tumor biological factors may predict response to different chemotherapy regimens with distinct mechanisms of action. (lu.se)
  • The results of our phenotype analysis also indicate that it is more likely that a panel of tumor biological factors instead of only one single factor may be needed for better prediction of chemotherapy response. (lu.se)
  • Moreover, the biological factors that determine the tissue-specificity of these tumors have not been identified. (ed.ac.uk)
  • Figure 2: Telomere-dependent senescence. (nature.com)
  • Braig, M. & Schmitt, C. A. Oncogene-induced senescence: putting the brakes on tumor development. (nature.com)
  • Senescence is generally considered to be a protective response: it is tumor suppressive and it limits the extent of fibrotic responses. (rupress.org)
  • This paper focuses on our increased, though by no means complete, understanding of the vitamin-D-dependent antimicrobial pathway and attempts to adjudicate published evidence regarding the vitamin's alleged role in altering host susceptibility to infections. (hindawi.com)
  • The phosphatidyl inositol 3-kinase (PI3K)/Akt pathway was involved in this ubiquitin-proteasome-mediated degradation of PDCD4. (plos.org)
  • This study provides a molecular explanation as to why tumors are resistant to the anti-proliferative effect of TGF-b in the absence of mutations in the TGF-b signaling pathway. (tmc.edu)
  • Here, we report that telomere capping is monitored at the G2/M transition by the p53/p21 damage response pathway. (ox.ac.uk)