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Caspase-8: Fly or Die

West Virginia University, Mary Babb Randolph Cancer Center, Morgantown, West Virginia

Requests for reprints: Steven M. Frisch, West Virginia University, Mary Babb Randolph Cancer Center, 1 Medical Center Drive, Campus Box 9300 Morgantown, WV 26506. Phone: 304-293-2980; E-mail: sfrisch{at}hsc.wvu.edu.

Key Words: caspase-8 • migration

Recent studies have revealed that procaspase-8 has an important function in cell adhesion and motility. Src phosphorylation controls this function by preventing the conversion of procaspase-8, which is an adhesion/migration factor, to mature caspase-8, which is an apoptosis-inducing factor. This provides a mechanism to switch these opposing functions. In its migratory role, procaspase-8 interacts with the phosphatidylinositol-3-OH kinase regulatory subunit p85 and c-src to modulate signaling by Rac and extracellular signal-regulated kinase, and promote calpain activation. Here, I survey the findings of these studies and discuss potential mechanisms and ramifications for cancer prognosis and therapy. [Cancer Res 2008;68(12):4491–3]

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