Cancer Institute A national cancer institute
designated cancer center

Matthew Bogyo

Publication Details

  • Caspase-8 Association with the Focal Adhesion Complex Promotes Tumor Cell Migration and Metastasis CANCER RESEARCH Barbero, S., Mielgo, A., Torres, V., Teitz, T., Shields, D. J., Mikolon, D., Bogyo, M., Barila, D., Lahti, J. M., Schlaepfer, D., Stupack, D. G. 2009; 69 (9): 3755-3763

    Abstract:

    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.

    View details for DOI 10.1158/0008-5472.CAN-08-3937

    View details for Web of Science ID 000265761900006

    View details for PubMedID 19383910

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