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. Author manuscript; available in PMC: 2011 Apr 1.
Published in final edited form as: Mol Aspects Med. 2010 Feb 11;31(2):205–214. doi: 10.1016/j.mam.2010.02.001

Figure 2.

Figure 2

Programming anoikis induction. Upon cell detachment, anoikis signaling can be activated via three major pathways. (1), death receptor mediated pathway, (2), ECM-integrin cell survival pathway and (3), mitochondrial mediated pathway. (1), Activation of FAS/FADD in death receptor induces cleavage of caspase-8 and subsequently activate downstream caspase-3 to induce apoptosis. (2) ECM-epithelial cell interaction mediates integrin dependent activation of Talin1, FAK/SRC and ILK-1. Activation of ILK-1 mediates phosphorylation of GSK3β and recruitment of Snail. This signaling cascade activates PI3K/AKT cell survival signals. Loss of survival signals upon cell detachment, enhances cell susceptibility to apoptotic stimuli. (3). Cell detachment induces upregulation of pro-apoptotic protein, like Bim and down regulation of anti-apoptotic regulatory proteins such as BCL-2, which activate the cytochrome-C release from the mitochondria and subsequently trigger activation of Caspase-9 and 3 to induce apoptosis.