FAK engages multiple pathways to maintain survival of fibroblasts and epithelia: differential roles for paxillin and p130Cas.
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.
Zouq
Nadia K
NK
Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, UK.
Keeble
James A
JA
Lindsay
Jennefer
J
Valentijn
Anthony J
AJ
Zhang
Lu
L
Mills
Deborah
D
Turner
Christopher E
CE
Streuli
Charles H
CH
Gilmore
Andrew P
AP
D000818:Animals; D023102:Anoikis / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D050719:Crk-Associated Substrate Protein / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology*; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D051419:Paxillin / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
C493842:Bcar1 protein, mouse; D050719:Crk-Associated Substrate Protein; D051419:Paxillin; C496062:Pxn protein, mouse; D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse