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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Barbero S,Mielgo A,Torres V,Teitz T,Shields DJ,Mikolon D,Bogyo M,Barilà D,Lahti JM,Schlaepfer D,Stupack DGdoi
10.1158/0008-5472.CAN-08-3937subject
Has Abstractpub_date
2009-05-01 00:00:00pages
3755-63issue
9eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-08-3937journal_volume
69pub_type
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