IAP Regulation of Metastasis

Swarna Mehrotra, Lucia R. Languino, Christopher M. Raskett, Arthur M. Mercurio, Takehiko Dohi, Dario C. Altieri

Research output: Contribution to journalArticle

213 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)53-64
Number of pages12
JournalCancer Cell
Volume17
Issue number1
DOIs
StatePublished - Jan 19 2010

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cell Biology
  • Cancer Research

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    Mehrotra, S., Languino, L. R., Raskett, C. M., Mercurio, A. M., Dohi, T., & Altieri, D. C. (2010). IAP Regulation of Metastasis. Cancer Cell, 17(1), 53-64. https://doi.org/10.1016/j.ccr.2009.11.021