期刊
CANCER CELL
卷 15, 期 5, 页码 416-428出版社
CELL PRESS
DOI: 10.1016/j.ccr.2009.03.016
关键词
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资金
- ACS [IRG-110376]
- Susan G. Komen Foundation [KGO81310]
- NCI [RO1-CA125454]
- NIH [R01 CA104748, R01 DK48498, T32CA117834]
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 TNF alpha through the activation of the NF-kappa B pathway. We demonstrated that NF-kappa B 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-kappa B 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.
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