FLICE / caspase - 8 activation triggers anoikis induced by β 1 - integrin blockade in human keratinocytes

Apoptosis that occurs following detachment of a cell from the extracellular matrix (ECM) has been termed anoikis (Frisch and Screaton, 2001). This mode of cell death has been observed in numerous adherent cells, such as endothelial cells (Meredith et al. Disturbances of anoikis can be involved in the alteration of tissue physiology, such as in intestinal epithelial cell homeostasis (von Herbay and Rudi, 2000) and in several disease states (Grossman, 2002). The acquisition of anoikis resistance is regarded as a crucial step in the metastatic transformation of a tumor (Yawata et al., 1998; Windham et al., 2002). Cell attachment not only provides structural anchorage for a cell, but it can initiate a cascade of survival signals. The anchorage of cells to the ECM is mediated mainly by integrins, and integrin signaling controls cell death in many cell settings (Giancotti and Ruoslahti, 1999). Integrins mediate survival in nontransforming cells, ensuring tissue homeostasis (Howlett et al., 1995) and during neoplastic transformation (Manzotti et al., 2000). On integrin ligation, focal adhesion-kinase (FAK) is phosphorylated and initiates a complex cascade of signaling molecules (Cary et al., 1999).