Caspases are proteolytic enzymes involved in committing apoptosis, but through the studies of knockout phenotypes in mice and Drosophila , it has been speculated that caspases might possess additional non-apoptotic functions.

We have found non-apoptotic functions for caspase-8 in both normal and tumor cell lines. Specifically, we found that caspase-8 promotes cell migration, adhesion, and Rac activation. Subsequently, we also found that caspase-8 interacts with the p85 subunit of PI3K. Accompanying stimulation of motility with epidermal growth factor the phosphorylation of caspase-8 on tyrosine-380 is induced and this phosphorylation allows for p85 interaction, cell migration, adhesion, and Rac activation. Caspase-8 also promoted EGF-induced Erk activation, stimulating cell migration.

Non-apoptotic functions also exist for caspase-2. We demonstrate that caspase-2 promotes cell-matrix adhesion, focal contact formation and FAK phosphorylation. Caspase 2 also mediates stress fiber dissolution in response to protein kinase-C activation. Insights into the mechanism whereby caspase 2 influences cytoskeletal processes with emphasis on Rho/ROCK/LIMK/cofilin and Rho/ROCK/MLC pathways are discussed.

These findings demonstrate a non-apoptotic function of a caspase involving signaling protein interactions rather than proteolysis. This is also the first report that caspase-2 and caspase-8 may mediate cytoskeletal functions independent of cell death.