An inappropriate ECM environment can induce a form of apoptosis termed anoikis. Several studies using a variety of cell types have shown that focal adhesion kinase (FAK), a key mediator of integrin signalling, has a crucial role in suppressing anoikis – but many different integrins can activate FAK, so how are the cell-type-specific effects regulated? On , Andrew Gilmore, Charles Streuli and colleagues use a constitutively active form of FAK to examine the mechanism by which FAK signals to suppress anoikis in mouse fibroblasts and epithelial cells, which have distinct embryonic lineages. The authors show that ECM-derived survival signals are commonly transduced by FAK in fibroblasts and epithelial cells, but the activation of FAK is interpreted differently in each cell type. The adaptor protein p130cas is shown to be a key downstream component of the FAK signalling pathway, promoting survival in fibroblasts but not in epithelial cells, in agreement with previous studies. By contrast, however, paxillin binding and tyrosine-925 phosphorylation of FAK are crucial events that are associated with FAK-dependent survival in epithelial cells. Thus, the authors conclude, cellular context is an important aspect in determining how the same survival signal is interpreted intracellularly.
