Document Detail


A study of death by anoikis in cultured epithelial cells.
MedLine Citation:
PMID:  11529878     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Epithelial cells are critically dependent upon cell-matrix and cell-cell adhesion for growth and survival. Anoikis is programmed cell death caused by disruption of cell-substrate adhesion in normal epithelial cells.
METHODS: We studied the induction of anoikis in vitro in two cell lines; HaCaT and SW742. PI3K, JAK2 and PKC are key elements in signalling pathways regulating cell survival, and using specific inhibitors we also examined their potential role in the induction of anoikis.
RESULTS: When prevented from adhesion by culture on polyHEMA, HaCaT cells underwent apoptosis selectively from the proliferating population; surviving cells underwent cell cycle arrest. In SW742 cells anoikis also occurred, but was balanced by increased cycling. The effects of specific kinase inhibitors indicated that both Janus kinase 2 and protein kinase C partially protect HaCaT cells from anoikis through inducing cell cycle arrest of surviving nonadherent cells; inhibition of Phosphatidylinositol 3-kinase did not induce cycling in HaCaTs prevented from adhesion but did stimulate anoikis. SW742 cells showed markedly different responses: Janus kinase 2 inhibition activated apoptosis directly, Phosphatidylinositol 3-kinase inhibition stimulated both cell cycling and apoptosis, while protein kinase C inhibition stimulated cycling but inhibited apoptosis.
CONCLUSIONS: Susceptibility to cell death in adhesion-prevented epithelial cells may thus be regulated by signalling pathways involving Phosphatidylinositol 3-kinase, Janus kinase 2 and protein kinase C. The ability of epithelial tumour cells to invade and metastasize may therefore result from disruption of these pathways.
Authors:
A J Bretland; J Lawry; R M Sharrard
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell proliferation     Volume:  34     ISSN:  0960-7722     ISO Abbreviation:  Cell Prolif.     Publication Date:  2001 Aug 
Date Detail:
Created Date:  2001-08-31     Completed Date:  2001-09-13     Revised Date:  2012-06-05    
Medline Journal Info:
Nlm Unique ID:  9105195     Medline TA:  Cell Prolif     Country:  England    
Other Details:
Languages:  eng     Pagination:  199-210     Citation Subset:  IM    
Affiliation:
Royal Holloway, University of London, UK.
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MeSH Terms
Descriptor/Qualifier:
Anoikis / physiology*
Apoptosis
Bromodeoxyuridine / metabolism,  pharmacokinetics
Carcinoma / drug therapy,  metabolism*,  pathology
Cell Adhesion / drug effects,  physiology
Cell Cycle / drug effects
Cell Line
Cell Survival / drug effects,  physiology
Colonic Neoplasms / drug therapy,  metabolism*,  pathology
Enzyme Inhibitors / pharmacology
Epithelial Cells / cytology,  drug effects,  metabolism*
Humans
Janus Kinase 2
Keratinocytes / cytology,  drug effects,  metabolism*
Phosphatidylinositol 3-Kinases / antagonists & inhibitors,  metabolism
Polyhydroxyethyl Methacrylate / pharmacology
Protein Kinase C / antagonists & inhibitors,  metabolism
Protein-Tyrosine Kinases / antagonists & inhibitors,  metabolism
Proto-Oncogene Proteins*
Signal Transduction / drug effects,  physiology
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Proto-Oncogene Proteins; 25249-16-5/Polyhydroxyethyl Methacrylate; 59-14-3/Bromodeoxyuridine; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.10.1/Janus Kinase 2; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.10.2/JAK2 protein, human; EC 2.7.11.13/Protein Kinase C

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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