| First Author | Barbero S | Year | 2009 |
| Journal | Cancer Res | Volume | 69 |
| Issue | 9 | Pages | 3755-63 |
| PubMed ID | 19383910 | Mgi Jnum | J:148268 |
| Mgi Id | MGI:3844169 | Doi | 10.1158/0008-5472.CAN-08-3937 |
| Citation | Barbero S, et al. (2009) Caspase-8 association with the focal adhesion complex promotes tumor cell migration and metastasis. Cancer Res 69(9):3755-63 |
| abstractText | Caspase-8 is a proapoptotic protease that suppresses neuroblastoma metastasis by inducing programmed cell death. Paradoxically, caspase-8 can also promote cell migration among nonapoptotic cells; here, we show that caspase-8 can promote metastasis when apoptosis is compromised. Migration is enhanced by caspase-8 recruitment to the cellular migration machinery following integrin ligation. Caspase-8 catalytic activity is not required for caspase-8-enhanced cell migration; rather, caspase-8 interacts with a multiprotein complex that can include focal adhesion kinase and calpain 2 (CPN2), enhancing cleavage of focal adhesion substrates and cell migration. Caspase-8 association with CPN2/calpastatin disrupts calpastatin-mediated inhibition of CPN2. In vivo, knockdown of either caspase-8 or CPN2 disrupts metastasis among apoptosis-resistant tumors. This unexpected molecular collaboration provides an explanation for the continued or elevated expression of caspase-8 observed in many tumors. |
