Stabilization of snail by NF-kappaB is required for inflammation-induced cell migration and invasion.
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 TNFalpha through the activation of the NF-kappaB pathway. We demonstrated that NF-kappaB 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-kappaB 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.
Mesh Terms:
Animals, Cell Line, Tumor, Cell Movement, Cell Transformation, Neoplastic, Female, Glycogen Synthase Kinase 3, Humans, Inflammation, Macrophages, Mice, Multiprotein Complexes, NF-kappa B, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasms, Peptide Hydrolases, SKP Cullin F-Box Protein Ligases, Signal Transduction, Transcription Factors, Tumor Necrosis Factor-alpha
Animals, Cell Line, Tumor, Cell Movement, Cell Transformation, Neoplastic, Female, Glycogen Synthase Kinase 3, Humans, Inflammation, Macrophages, Mice, Multiprotein Complexes, NF-kappa B, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasms, Peptide Hydrolases, SKP Cullin F-Box Protein Ligases, Signal Transduction, Transcription Factors, Tumor Necrosis Factor-alpha
Cancer Cell
Date: May. 05, 2009
PubMed ID: 19411070
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