USP24 promotes drug resistance during cancer therapy

Shao-An Wang, Ming-Jer Young, Yi Chang Wang, Shu Hui Chen, Chia Yu Liu, Yao An Lo, Hung Hsiang Jen, Kai Cheng Hsu, Jan Jong Hung

Research output: Contribution to journalArticlepeer-review

Abstract

Drug resistance has remained an important issue in the treatment and prevention of various diseases, including cancer. Herein, we found that USP24 not only repressed DNA-damage repair (DDR) activity by decreasing Rad51 expression to cause the tumor genomic instability and cancer stemness, but also increased the levels of the ATP-binding cassette (ABC) transporters P-gp, ABCG2, and ezrin to enhance the pumping out of Taxol from cancer cells, thus resulted in drug resistance during cancer therapy. A novel USP24 inhibitor, NCI677397, was screened for specific inhibiting the catalytic activity of USP24. This inhibitor was identified to suppress drug resistance via decreasing genomic instability, cancer stemness, and the pumping out of drugs from cancer cells. Understanding the role and molecular mechanisms of USP24 in drug resistance will be beneficial for the future development of a novel USP24 inhibitor. Our studies provide a new insight of USP24 inhibitor for clinically implication of blocking drug resistance during chemotherapy.

Original languageEnglish
JournalCell Death and Differentiation
DOIs
Publication statusAccepted/In press - 2021

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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