Open AccessFAK engages multiple pathways to maintain survival of fibroblasts and epithelia – differential roles for paxillin and p130Cas
Author(s) -
Nadia K. Zouq,
James A. Keeble,
Jennefer Lindsay,
Anthony Valentijn,
Lu Zhang,
Deborah Mills,
Christopher E. Turner,
Charles Streuli,
Andrew Gilmore
Publication year - 2009
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.030478
Subject(s) - anoikis , paxillin , focal adhesion , biology , microbiology and biotechnology , integrin , extracellular matrix , programmed cell death , cell type , ptk2 , cell , cell adhesion , apoptosis , signal transduction , kinase , protein kinase a , genetics , mitogen activated protein kinase kinase
Different cell types interpret their distinct extracellular matrix (ECM) environments to bring about specific cell fate decisions, and can differentiate or undergo apoptosis depending on their local adhesive interactions. Apoptosis in response to an inappropriate ECM environment is termed `anoikis', or homelessness. Several studies, utilising a variety of cell types, have indicated a common, crucial role for focal adhesion kinase (FAK) in suppressing anoikis. A wide range of different integrins can activate FAK, raising the question of how cell type specific effects are regulated. In this study, we have used a constitutively active form of FAK to examine the mechanism of FAK-mediated survival signalling in cell types from distinct embryonic lineages that show differing sensitivities to anoikis. We demonstrate that both fibroblasts and epithelial cells prevent anoikis through FAK activation. We show that FAK activates multiple downstream pathways in order to suppress anoikis. However FAK regulates survival through a more restricted set of pathways in the more anoikis-sensitive epithelial cells. Furthermore, we identify a novel role for paxillin in apoptosis suppression.