Control of adhesion-dependent cell survival by focal adhesion kinase.
Open Access
- 1 August 1996
- journal article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 134 (3), 793-799
- https://doi.org/10.1083/jcb.134.3.793
Abstract
The interactions of integrins with extracellular matrix proteins can activate focal adhesion kinase (FAK) and suppress apoptosis in normal epithelial and endothelial cells; this subset of apoptosis has been termed "anoikis." Here, we demonstrate that FAK plays a role in the suppression of anoikis. Constitutively activated forms of FAK rescued two established epithelial cell lines from anoikis. Both the major autophosphorylation site (Y397) and a site critical to the kinase activity (K454) of FAK were required for this effect. Activated FAK also transformed MDCK cells, by the criteria of anchorage-independent growth and tumor formation in nude mice. We provide evidence that this transformation resulted primarily from the cells' resistance to anoikis rather than from the activation of growth factor response pathways. These results indicate that FAK can regulate anoikis and that the conferral of anoikis resistance may suffice to transform certain epithelial cells.Keywords
This publication has 31 references indexed in Scilit:
- Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient miceNature, 1995
- c-Src enhances the spreading of src-/- fibroblasts on fibronectin by a kinase-independent mechanism.Genes & Development, 1995
- Signal transduction through integrins: A central role for focal adhesion kinase?BioEssays, 1995
- Integrin αvβ3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vesselsCell, 1994
- Focal adhesion kinase and associated proteinsCurrent Opinion in Cell Biology, 1994
- Membrane targeting of the nucleotide exchange factor Sos is sufficient for activating the Ras signaling pathwayCell, 1994
- Apoptosis in human skin development: Morphogenesis, periderm, and stem cellsDevelopmental Dynamics, 1994
- Disruption of epithelial cell-matrix interactions induces apoptosisThe Journal of cell biology, 1994
- Identification of sequences required for the efficient localization of the focal adhesion kinase, pp125FAK, to cellular focal adhesions.The Journal of cell biology, 1993
- Adhesion molecules in cancer: the role of integrinsCurrent Opinion in Cell Biology, 1993