Stabilization of Snail by NF-κB Is Required for Inflammation-Induced Cell Migration and Invasion

Yadi Wu, Jiong Deng, Piotr G. Rychahou, Suimin Qiu, B. Mark Evers, Binhua P. Zhou

Research output: Contribution to journalArticle

541 Scopus citations

Abstract

The increased motility and invasiveness of tumor cells are reminiscent of epithelial-mesenchymal transition (EMT), which occurs during embryonic development, wound healing, and metastasis. In this study, we found that Snail is stabilized by the inflammatory cytokine TNFα through the activation of the NF-κB pathway. We demonstrated that NF-κB is required for the induction of COP9 signalosome 2 (CSN2), which, in turn, blocks the ubiquitination and degradation of Snail. Furthermore, we showed that the expression of Snail correlated with the activation of NF-κB in cancer cell lines and metastatic tumor samples. Knockdown of Snail expression inhibited cell migration and invasion induced by inflammatory cytokines and suppressed inflammation-mediated breast cancer metastasis. Our study provides a plausible mechanism for inflammation-induced metastasis.

Original languageEnglish (US)
Pages (from-to)416-428
Number of pages13
JournalCancer Cell
Volume15
Issue number5
DOIs
StatePublished - May 5 2009

Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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