INTEGRINS AND ANOIKIS

The loss of integrin-mediated cell-matrix contact induces apoptosis (' anoikis') in certain cell types. Recently it has been shown that prote in kinase signaling pathways control anoikis both positively and negat ively. Focal adhesion kinase, when activated by integrins, can suppres s anoikis. Phosphatidylinositol 3-kinase and the AKT oncoprotein may m ediate the anoikis-suppressing effects of focal adhesion kinase. Conve rsely, the stress-activated protein kinase/Jun amino-terminal kinase p athway promotes anoikis. Latest results indicate that caspase-mediated cleavage of the first component of this latter pathway, MEKK-1, may t rigger activation of this pathway in anoikis. In addition, certain int egrins may regulate bcl-2 expression levels, possibly adjusting the th reshold for anoikis.