USP1-WDR48 deubiquitinase complex enhances TGF-β induced epithelial-mesenchymal transition of TNBC cells via stabilizing TAK1.

Dianwen Han, Lijuan Wang, Bing Chen, Wenjing Zhao, Yiran Liang, Yaming Li, Hanwen Zhang, Ying Liu, Xiaolong Wang, Tong Chen, Chen Li, Xiaojin Song, Dan Luo, Zheng Li, Qifeng Yang

Cell cycle (Georgetown, Tex.) 2021 Feb

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Triple-negative breast cancer (TNBC) is the most aggressive histological subtype of breast cancer and is characterized by poor outcomes and a lack of specific-targeted therapies. Transforming growth factor-β (TGF-β) acts as the key cytokine in the epithelial-mesenchymal transition (EMT) and the metastasis of TNBC. However, the regulatory mechanisms of the TGF-β signaling pathway remain largely unknown. In this study, we identified that the USP1/WDR48 complex could effectively enhance TGF-β-mediated EMT and migration of TNBC cells. Furthermore, lower phosphorylation of Smad2/3, Erk, Jnk, and p38 was noted on the suppression of the expression of endogenous USP1 or WDR48. Moreover, the USP1-WDR48 complex was found to downregulate the polyubiquitination of TAK1 and mediate its in vitro stability. Therefore, our findings have shed a light on the novel role of the USP1/WDR48 complex in promoting TGF-β-induced EMT and migration in TNBC via in vitro stabilization of TAK1.

Citation

Dianwen Han, Lijuan Wang, Bing Chen, Wenjing Zhao, Yiran Liang, Yaming Li, Hanwen Zhang, Ying Liu, Xiaolong Wang, Tong Chen, Chen Li, Xiaojin Song, Dan Luo, Zheng Li, Qifeng Yang. USP1-WDR48 deubiquitinase complex enhances TGF-β induced epithelial-mesenchymal transition of TNBC cells via stabilizing TAK1. Cell cycle (Georgetown, Tex.). 2021 Feb;20(3):320-331