Document Detail

A transient increase in the activity of Src-family kinases induced by cell detachment delays anoikis of intestinal epithelial cells.
MedLine Citation:
PMID:  15674335     Owner:  NLM     Status:  MEDLINE    
Detachment of epithelial cells from the basement membrane (BM) induces apoptosis, a phenomenon now widely known as anoikis. Studies in mammary and intestinal epithelial cells have shown that the loss of attachment to the BM rapidly triggers reversible proapoptotic events from which the cells can recover if they reattach within a certain period. Thus, cells seem to be transiently protected from the initial detachment-induced proapoptotic events. The molecular mechanisms underlying such transient protection against anoikis are unknown. In this paper, we present evidence indicating that detachment of intestinal epithelial cells triggers a transient, yet significant increase in the activity of the tyrosine kinases c-Src and c-Fyn, and that this activation of Src-family kinases (SFK) contributes to the transient protection against anoikis in these cells. The protective signals from SFK are mediated by the PI3K pathway, and caveolin-1. In addition, we show that the MEK1-ERK1/2 pathway acts in a synergistic manner with SFK to protect intestinal epithelial cells from anoikis.
Mariano Andres Loza-Coll; Sheron Perera; Wen Shi; Jorge Filmus
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Oncogene     Volume:  24     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-03-03     Completed Date:  2005-03-24     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  1727-37     Citation Subset:  IM    
Division of Molecular and Cellular Biology, Sunnybrook and Women's College Health Sciences Center, Department of Medical Biophysics, University of Toronto, 2075 Bayview Avenue, S Wing, Room S218, Toronto, ON, Canada M4N 3M5.
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MeSH Terms
1-Phosphatidylinositol 3-Kinase / physiology
Cell Adhesion
Cells, Cultured
Intestinal Mucosa / cytology*
MAP Kinase Kinase 1 / physiology
Mitogen-Activated Protein Kinase 1 / physiology
Mitogen-Activated Protein Kinase 3 / physiology
Pyrazoles / pharmacology
Pyrimidines / pharmacology
src Homology Domains
src-Family Kinases / physiology*
Reg. No./Substance:
0/4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine; 0/Pyrazoles; 0/Pyrimidines; EC 3-Kinase; EC Kinases; EC Protein Kinase 1; EC Protein Kinase 3; EC Kinase Kinase 1

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