Cancer Cell, Volume 17, Issue 1, 53-64, 19 January 2010 | Copyright © 2010 Elsevier Inc. All rights reserved. | 10.1016/j.ccr.2009.11.021
Swarna Mehrotra, Lucia R. Languino, Christopher M. Raskett, Arthur M. Mercurio, Takehiko Dohi, Dario C. Altieri
* Highlights
* Inhibitor-of-Apoptosis (IAP) proteins mediate tumor cell invasion and metastasis
* This pathway requires NF-κB activation and is independent of IAP cytoprotection
* IAP tumor cell invasion involves signaling by fibronectin-β1 integrin and FAK, Src.
* Summary
* Inhibitor-of-Apoptosis (IAP) proteins contribute to tumor progression, but the requirements of this pathway are not understood. Here, we show that intermolecular cooperation between XIAP and survivin stimulates tumor cell invasion and promotes metastasis. This pathway is independent of IAP inhibition of cell death. Instead, a survivin-XIAP complex activates NF-κB, which in turn leads to increased fibronectin gene expression, signaling by β1 integrins, and activation of cell motility kinases FAK and Src. Therefore, IAPs are direct metastasis genes, and their antagonists could provide antimetastatic therapies in patients with cancer.
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