USP20 positively regulates tumorigenesis and chemoresistance through β-catenin stabilization. Issue 10 (November 2018)

• Record Type: Journal Article
• Authors: Wu, Chenming; Luo, Kuntian; Zhao, Fei; Yin, Ping; Song, Ying; Deng, Min; Huang, Jinzhou; Chen, Yuping; Li, Lei; Lee, SeungBaek; Kim, JungJin; Zhou, Qin; Tu, Xinyi; Nowsheen, Somaira; Luo, Qifeng; Gao, Xiumei; Lou, Zhenkun; Liu, Zhongmin; Yuan, Jian
• Is Part Of: Cell death and differentiation. Volume 25:Issue 10(2018)
• Page Start: 1855
• Page End: 1869
• Publication Date: 2018-11
• Subjects: Cell death -- Periodicals; Cell differentiation -- Periodicals; 571.835
• DOI: 10.1038/s41418-018-0138-z
• Languages: English
• ISSNs: 1350-9047

Abstract

Abstract β-catenin is a major transcriptional activator of the canonical Wnt/β-catenin signaling pathway. It is important for a series of biological processes including tissue homeostasis, and embryonic development and is involved in various human diseases. Elevated oncogenic activity of β-catenin is frequently observed in cancers, which contributes to survival, metastasis and chemo-resistance of cancer cells. However, the mechanism of β-catenin overexpression in cancers is not well defined. Here we demonstrate that the deubiquitination enzyme USP20 is a new regulator of the Wnt/β-catenin signaling pathway. Mechanistically, USP20 regulates the deubiquitination of β-catenin to control its stability, thereby inducing proliferation, invasion and migration of cancer cells. High expression of USP20 correlates with increased β-catenin protein level in multiple cancer cell lines and patient samples. Moreover, knockdown of USP20 increases β-catenin polyubiquitination, which enhances β-catenin turnover and cell sensitivity to chemotherapy. Collectively, our results establish the USP20-β-catenin axis as a critical regulatory mechanism of canonical Wnt/β-catenin signaling pathway with an important role in tumorigenesis and chemo response in human cancers.