USP20 positively regulates tumorigenesis and chemoresistance through β-catenin stabilization

• DOI: 10.1038/s41418-018-0138-z
• Publication Date: 2018-06-04T08:33:28Z
• Authors: Chenming Wu; Kuntian Luo; Fei Zhao; Ping Yin; Ying Song; Min Deng; Jinzhou Huang; Yuping Chen; Lei Li; SeungBaek Lee; JungJin Kim; Qin Zhou; Xinyi Tu; Somaira Nowsheen; Qifeng Luo; Xiumei Gao; Zhenkun Lou; Zhongmin Liu; Jian Yuan
• Keywords: Deubiquitinating enzyme; Beta-catenin

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.