The caspases are a family of ubiquitously expressed cysteine proteases best known for their roles in
programmed cell death. However, caspases play a number of other roles in vertebrates. In the case of
caspase-8, loss of expression is an embryonic lethal phenotype, and caspase-8 plays roles in suppressing
cellular necrosis, promoting differentiation and immune signaling, regulating autophagy, and promoting cellular
migration. Apoptosis and migration require localization of caspase-8 in the periphery of the cells, where
caspase-8 acts as part of distinct biosensory complexes that either promote migration in appropriate cellular
microenvironments, or cell death in inappropriate settings. In the cellular periphery, caspase-8 interacts with
components of the focal adhesion complex in a tyrosine-kinase dependent manner, promoting both cell
migration in vitro and metastasis in vivo. Mechanistically, caspase-8 interacts with components of both focal
adhesions and early endosomes, enhancing focal adhesion turnover and promoting rapid integrin recycling to
the cell surface. Clinically, this suggests that the expression of caspase-8 may not always be a positive
prognostic sign, and that the role of caspase-8 in cancer progression is likely context-dependent.
Calpain, caspase 8, cell migration, nonapoptotic, phosphorylation, SH2 domain.
University of California San Diego, Moores Cancer Center, Department of Reproductive Medicine, 0803, 3855 Health Sciences Dr., La Jolla, CA 92093, USA.