Stabilization of Snail by NF-κB Is Required for Inflammation-Induced Cell Migration and Invasion
By Yadi Wu, Jiong Deng, P. Rychahou, S. Qiu, B. Evers, Binhua P. Zhou. Cancer Cell, 2009
795 citations recorded by the source corpus.
SUMMARY The increased motility and invasiveness of tumor cells are reminiscent of epithelial-mesenchymal transition (EMT) that 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.
Subfields: Genetics, Hepatology, Oncology
View Paper: https://www.semanticscholar.org/paper/23807168a2c68ec3a5d2a2aae158cc8b3d24ee1f
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Citations in the corpus
- Epithelial–mesenchymal plasticity in carcinoma metastasis (2013, background): “The inflammatory cytokine TNFa can stabilize Snail1 via NF-kB activation (Wu et al. 2009) and induce Twist1 expression via IKK-b and NF-kB p65 activation (Li et al. 2012).”
- Cancer-Associated Fibroblasts Are Activated in Incipient Neoplasia to Orchestrate Tumor-Promoting Inflammation in an NF-kappaB-Dependent Manner. (2010, background): “NF-kB is known to play a central role in mediating protumorigenic inflammatory signaling, but its activity has previously been ascribed to macrophages or cancer cells (Bollrath et al., 2009; Grivennikov et al., 2009; Wu et al., 2009).”
- NF-κB, an Active Player in Human Cancers (2014, positive): “Snail, a zinc-finger transcription repressor, on the other hand, is stabilized by the COP9 signalosome 2 (CSN2), a protein complex in the ubiquitin-proteasome pathway that contributes to NF-κ B activation in inflammation-induced cell migration and invasion (33).”
- Deubiquitination and Stabilization of PD-L1 by CSN5 (2016, methodology): “For instance, deubiquitination of HSP70 and Snail by CSN5were reported tomodulate exosomal protein sorting (Liu et al., 2009) and to enhance cancer cell invasion and (E) Intracellular cytokine staining of IFN-g+CD8+ in CD3+ T cell populations from 4 experiment.”
- Epithelial-mesenchymal transitions in development and disease. (2009, background): “Snail1 protein stabilization is promoted by NFκB, which prevents its phosphorylation by GSK-3 and subsequent degradation (Wu et al., 2009a), whereas the formation of a ternary complex between wild-type p53, the ubiquitin ligase Mdm2, and Snail2 triggers its degradation (Wang et al., 2009a).”
- The Role of Snail in EMT and Tumorigenesis (2013, background): “Our study shows that Snail is stabilized by the TNF-α/NF-κB pathway through the induction of CSN2, which blocks the phosphorylation and ubiquitination of Snail by disrupting its binding to GSK-3β and β-Trcp [51].”
- Rac and Rho GTPases in cancer cell motility control (2010, background): “Tumor microenvironmental cues as inflammation [75] or stromal fibroblasts (Chiarugi, P.”
- Tumor-associated macrophages in tumor metastasis: biological roles and clinical therapeutic applications (2019, background): “Biologically, macrophages participate in the EMT process via secreting various soluble factors, such as IL1β, IL-8, TNF-α, and transforming growth factor-β (TGF-β) [80, 83, 84].”