IAP regulation of metastasis
Department of Cancer Biology
Animals; Blotting, Western; Cell Line, Tumor; Female; Humans; Inhibitor of Apoptosis Proteins; Male; Mice; Microtubule-Associated Proteins; *Neoplasm Invasiveness; RNA, Small Interfering; Signal Transduction
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-kappaB, which in turn leads to increased fibronectin gene expression, signaling by beta1 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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Citation: Cancer Cell. 2010 Jan 19;17(1):53-64. Link to article on publisher's site