The deubiquitinase USP9X promotes tumor cell survival and confers chemoresistance through YAP1 stabilization

Lei Li, Tongzheng Liu, Yunhui Li, Chenming Wu, Kuntian Luo, Yujiao Yin, Yuping Chen, Somaira Nowsheen, Jinhuan Wu, Zhenkun Lou, Jian Yuan

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

The Yes-Associated protein 1 (YAP1), a major downstream effector of the Hippo pathway, functions as a transcriptional regulator and has an important role in cellular control of organ size and tumor growth. Elevated oncogenic activity of YAP1 has been clarified in different types of human cancers, which contributes to cancer cell survival and chemoresistance. However, the molecular mechanism of YAP1 overexpression in cancer is still not clear. Here we demonstrate that the deubiquitination enzyme USP9X deubiquitinates and stabilizes YAP1, thereby promoting cancer cell survival. Increased USP9X expression correlates with increased YAP1 protein in human breast cancer cell lines and patient samples. Moreover, depletion of USP9X increases YAP1 polyubiquitination, which in turn elevates YAP1 turnover and cell sensitivity to chemotherapy. Overall, our study establishes the USP9X-YAP1 axis as an important regulatory mechanism of breast cancer and provides a rationale for potential therapeutic interventions in the treatment of breast cancer.

Original languageEnglish (US)
Pages (from-to)2422-2431
Number of pages10
JournalOncogene
Volume37
Issue number18
DOIs
StatePublished - May 1 2018

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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