Signalling mechanisms of anoikis

Abstract

Apoptosis following loss of cell anchorage ('anoikis') is of relevance for development, tissue homeostasis and disease. Integrins regulate cell viability through their interaction with the extracellular matrix and they can sense mechanical forces arising from the matrix and convert these stimuli to chemical signals capable of modulating intracellular signal transduction. Recently it has been shown that protein kinase signalling pathways and apoptosis-related molecular control anoikis both positively and negatively. Focal adhesion kinase, when activated by integrins, can suppress anoikis. Phosphatidylinositol 3-kinase/Akt and mitogenactivated protein kinase may mediate the anoikissuppressing effects of cells. Conversely, the stressactivated protein kinase/Jun amino-terminal kinase pathway promotes anoikis. In addition, certain bcl-2 and bcl-2-related proteins may also participate in the regulating of anoikis. In this review, molecular mechanisms of signal pathway inducing and perpetuating detachment-induced apoptosis will be discussed with special emphasis on the role of integrins, focal adhesion kinase, phosphatidylinositol 3- kinase/Akt, mitogen-activated protein kinase and bcl-2 family members.