Fig. 2.

Pathway diagram of internal and external mechanisms of anoikis. Lack of ECM exposure or inappropriate ECM exposure fails to activate pro-survival signaling, leading to a reduction in the anti-apoptotic pathway and, thus, activation of extrinsic death receptors and intrinsic integrin-mediated mitochondria-dependent anoikis. The death receptor pathway triggers two different extrinsic pathways in different cell types: type 1 leads to direct proteolysis of the target dependent on caspase-7 activation; type 2, which aggregates in the intrinsic pathway through a truncated form of Bid (tBid), promotes the release of mitochondrial cytochrome c and assembly of apoptotic corpuscles. These events induce proteolysis of caspase-specific targets, thereby promoting anoikis