The study investigates the role of focal adhesion kinase (FAK) in suppressing anoikis, a subset of apoptosis that occurs in normal epithelial and endothelial cells when they are detached from the extracellular matrix. The authors demonstrate that activated forms of FAK can rescue epithelial cell lines from anoikis, with both the major autophosphorylation site (Y397) and a site critical to kinase activity (K454) being essential for this effect. They use a chimeric protein, CD2-FAK, which retains tyrosine 397 autophosphorylation and full tyrosine kinase activity in suspended cells. CD2-FAK is constitutively activated in MDCK cells and accelerates cell spreading on collagen. Expression of CD2-FAK confers anoikis resistance and anchorage-independent growth, leading to tumorigenicity in nude mice. The study also shows that CD2-FAK controls anoikis but not growth factor responsiveness, suggesting that FAK may contribute to epithelial carcinogenesis by suppressing anoikis without altering growth factor response pathways.The study investigates the role of focal adhesion kinase (FAK) in suppressing anoikis, a subset of apoptosis that occurs in normal epithelial and endothelial cells when they are detached from the extracellular matrix. The authors demonstrate that activated forms of FAK can rescue epithelial cell lines from anoikis, with both the major autophosphorylation site (Y397) and a site critical to kinase activity (K454) being essential for this effect. They use a chimeric protein, CD2-FAK, which retains tyrosine 397 autophosphorylation and full tyrosine kinase activity in suspended cells. CD2-FAK is constitutively activated in MDCK cells and accelerates cell spreading on collagen. Expression of CD2-FAK confers anoikis resistance and anchorage-independent growth, leading to tumorigenicity in nude mice. The study also shows that CD2-FAK controls anoikis but not growth factor responsiveness, suggesting that FAK may contribute to epithelial carcinogenesis by suppressing anoikis without altering growth factor response pathways.