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Updated: Jun 23, 2026

Characterization of Cell Membrane Extensions and Studying Their Roles in Cancer Cell Adhesion Dynamics
Published on: March 26, 2018
Caspase-8 association with the focal adhesion complex promotes tumor cell migration and metastasis
Simone Barbero1, Ainhoa Mielgo, Vicente Torres
1Department of Pathology, Moores UCSD Cancer Center, University of California-San Diego, San Diego, California 92093, USA.
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.
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