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.

Barbero, S., Mielgo, A., Torres, V., Teitz, T., Shields, D., Mikolon, D., et al. (2009). Caspase-8 association with the focal adhesion complex promotes tumor cell migration and metastasis. CANCER RESEARCH, 69(9), 3755-3763 [10.1158/0008-5472.CAN-08-3937].

Caspase-8 association with the focal adhesion complex promotes tumor cell migration and metastasis

BARILA', DANIELA;
2009-01-01

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.
2009
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/18 - GENETICA
English
Con Impact Factor ISI
calpain 2; calpastatin; caspase 8; focal adhesion kinase; integrin; multiprotein complex; animal cell; apoptosis; article; cancer cell; catalysis; cell disruption; cell migration; controlled study; enzyme substrate; focal adhesion; human; human cell; in vivo study; metastasis; mouse; nonhuman; priority journal; protein cleavage; protein expression; protein protein interaction; tumor resistance; animals; calcium-binding proteins; calpain; cell line, tumor; cell movement; focal adhesion protein-tyrosine kinases; focal adhesions; humans; lung neoplasms; mice; transgenic; neoplasm metastasis; neuroblastoma; talin
http://cancerres.aacrjournals.org/content/69/9/3755.full.pdf#page=1&view=FitH
Barbero, S., Mielgo, A., Torres, V., Teitz, T., Shields, D., Mikolon, D., et al. (2009). Caspase-8 association with the focal adhesion complex promotes tumor cell migration and metastasis. CANCER RESEARCH, 69(9), 3755-3763 [10.1158/0008-5472.CAN-08-3937].
Barbero, S; Mielgo, A; Torres, V; Teitz, T; Shields, D; Mikolon, D; Bogyo, M; Barila', D; Lahti, J; Schlaepfer, D; Stupack, D
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/8001
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