Journal
CELL DEATH AND DIFFERENTIATION
Volume 28, Issue 9, Pages 2690-2707Publisher
SPRINGERNATURE
DOI: 10.1038/s41418-021-00778-z
Keywords
-
Categories
Funding
- National Cheng Kung University
- Ministry of Science and Technology of Taiwan
Ask authors/readers for more resources
USP24 plays a crucial role in repressing DNA-damage repair activity and increasing ABC transporters levels, leading to drug resistance. The novel USP24 inhibitor NCI677397 shows potential in suppressing drug resistance by targeting these mechanisms.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available