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

研究成果: 雜誌貢獻文章同行評審

1 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
期刊Cell Death and Differentiation
DOIs
出版狀態接受/付印 - 2021

ASJC Scopus subject areas

  • 分子生物學
  • 細胞生物學

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