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.
|Number of pages||13|
|State||Published - May 5 2009|
Bibliographical noteFunding Information:
We thank Dr. Warner C. Greene for providing wild-type and deletion mutants of p65. We also thank Dr. James R. Woodgett for providing immortalized wild-type and GSK-3β −/− MEFs. This work was supported by the John Sealy Memorial Endowment Fund, a pilot award from the ACS (IRG-110376), grants from the Susan G. Komen Foundation (KG081310) and NCI (RO1-CA125454) (to B.P.Z.), and grants RO1 CA104748 and RO1 DK48498 from the NIH (to B.M.E.). Y.W. was supported by postdoctoral fellowship from NIH (T32CA117834).
ASJC Scopus subject areas
- Cancer Research