Dub3 inhibition suppresses breast cancer invasion and metastasis by promoting Snail1 degradation
Open Access
- 15 February 2017
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 8 (1), 14228
- https://doi.org/10.1038/ncomms14228
Abstract
Snail1, a key transcription factor of epithelial–mesenchymal transition (EMT), is subjected to ubiquitination and degradation, but the mechanism by which Snail1 is stabilized in tumours remains unclear. We identify Dub3 as a bona fide Snail1 deubiquitinase, which interacts with and stabilizes Snail1. Dub3 is overexpressed in breast cancer; knockdown of Dub3 resulted in Snail1 destabilization, suppressed EMT and decreased tumour cell migration, invasion, and metastasis. These effects are rescued by ectopic Snail1 expression. IL-6 also stabilizes Snail1 by inducing Dub3 expression, the specific inhibitor WP1130 binds to Dub3 and inhibits the Dub3-mediating Snail1 stabilization in vitro and in vivo. Our study reveals a critical Dub3–Snail1 signalling axis in EMT and metastasis, and provides an effective therapeutic approach against breast cancer.This publication has 65 references indexed in Scilit:
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