CONTROL OF ADHESION-DEPENDENT CELL-SURVIVAL BY FOCAL ADHESION KINASE

The interactions of integrins with extracellular matrix proteins can a ctivate focal adhesion kinase (FAK) and suppress apoptosis in normal e pithelial and endothelial cells; this subset of apoptosis has been ter med ''anoikis.'' Here, we demonstrate that FAK plays a role in the sup pression of anoikis. Constitutively activated forms of FAK rescued two established epithelial cell lines from anoikis. Both the major autoph osphorylation site (Y397) and a site critical to the kinase activity ( K454) of FAK were required for this effect. Activated FAK also transfo rmed MDCK cells, by the criteria of anchorage-independent growth and t umor formation in nude mice. We provide evidence that this transformat ion resulted primarily from the cells' resistance to anoikis rather th an from the activation of growth factor response pathways. These resul ts indicate that FAK can regulate anoikis and that the conferral of an oikis resistance may suffice to transform certain epithelial cells.