Caspase-8 Promotes Cell Motility and Calpain Activity under Nonapoptotic Conditions

Abstract

Significant caspase-8 activity has been found in normal and certain tumor cells, suggesting that caspase-8 possesses an alternative, nonapoptotic function that may contribute to tumor progression. In this article, we report that caspase-8 promotes cell motility. In particular, caspase-8 is required for the optimal activation of calpains, Rac, and lamellipodial assembly. This represents a novel nonapoptotic function of caspase-8 acting at the intersection of the caspase-8 and calpain proteolytic pathways to coordinate cell death versus cell motility signaling. (Cancer Res 2006; 66(8): 4273-8)

Mutant PIK3CA licenses TRAIL and CD95L to induce non-apoptotic caspase-8-mediated ROCK activation

“…31 In addition, caspase-8 has also been found to be recruited to the focal adhesion complex in NB7 cells in which it enhances cell migration by stimulating talin cleavage by calpains in a caspase-activity/apoptosisindependent manner. 32,33 As Src and PI3K are part of the focal adhesion complex, it is tempting to speculate that Y380 phosphorylation of caspase-8 and activation of PI3K/Rac reflect a function of caspase-8 in the focal adhesion complex. Taken together, to date, there is no evidence that the migration-promoting functions of CD95 and/or caspase-8 require caspase-8 activity.…”

Caspases in apoptosis and beyond

“…Cell migration has been shown to be severely hampered in caspase-8-deficient MEFs. Caspase-8 activates calpains through a mechanism not yet clear and promotes subsequent cytoskeletal remodeling downstream of calpains (Helfer et al, 2006). A role of pro-inflammatory caspase in regulating cell migration was illustrated by the studies on caspase-11-mutant mice.…”

Impact of caspase activation in human spermatozoa

“…Sperm Parameters Although in nonapoptotic circumstances in somatic cells caspase-8 is known as promoter of cell motility (Helfer et al, 2006), in sperm several studies proved a negative correlation of caspase-3, -8, and -9 activation and progressive motility. This was true for fresh and cryopreserved-thawed semen samples from donors as well as infertility patients (Grunewald et al, 2001;Marchetti et al, 2004;Paasch et al, , 2004aTaylor et al, 2004;Said et al, 2006;Weng, 2002).…”