2. Academic Validation
  3. USP24 promotes drug resistance during cancer therapy

USP24 promotes drug resistance during cancer therapy

  • Cell Death Differ. 2021 Sep;28(9):2690-2707. doi: 10.1038/s41418-021-00778-z.
Shao-An Wang # 1 2,  Ming-Jer Young # 1,  Yi-Chang Wang 1,  Shu-Hui Chen 3,  Chia-Yu Liu 1,  Yao-An Lo 1,  Hung-Hsiang Jen 3,  Kai-Cheng Hsu 4,  Jan-Jong Hung 5 6
Affiliations

Affiliations

  • 1 Department of Biotechnology and Bioindustry Sciences, National Cheng Kung University, Tainan, Taiwan.
  • 2 School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan.
  • 3 Department of Chemistry, College of Science, National Cheng Kung University, Tainan, Taiwan.
  • 4 Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
  • 5 Department of Biotechnology and Bioindustry Sciences, National Cheng Kung University, Tainan, Taiwan. petehung@mail.ncku.edu.tw.
  • 6 Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan. petehung@mail.ncku.edu.tw.
  • # Contributed equally.
PMID: 33846536 DOI: 10.1038/s41418-021-00778-z
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.

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