USP20 positively regulates tumorigenesis and chemoresistance through β-catenin stabilization

Chenming Wu, Kuntian Luo, Fei Zhao, Ping Yin, Ying Song, Min Deng, Jinzhou Huang, Yuping Chen, Lei Li, Seung Baek Lee, Jung Jin Kim, Qin Zhou, Xinyi Tu, Somaira Nowsheen, Qifeng Luo, Xiumei Gao, Zhenkun Lou, Zhongmin Liu, Jian Yuan

Research output: Contribution to journalArticle

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1855-1869
Number of pages15
JournalCell Death and Differentiation
Volume25
Issue number10
DOIs
StatePublished - Nov 1 2018

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'USP20 positively regulates tumorigenesis and chemoresistance through β-catenin stabilization'. Together they form a unique fingerprint.

  • Cite this

    Wu, C., Luo, K., Zhao, F., Yin, P., Song, Y., Deng, M., Huang, J., Chen, Y., Li, L., Lee, S. B., Kim, J. J., Zhou, Q., Tu, X., Nowsheen, S., Luo, Q., Gao, X., Lou, Z., Liu, Z., & Yuan, J. (2018). USP20 positively regulates tumorigenesis and chemoresistance through β-catenin stabilization. Cell Death and Differentiation, 25(10), 1855-1869. https://doi.org/10.1038/s41418-018-0138-z