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USP24 promotes drug resistance during cancer therapy

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 i...

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Autores principales: Wang, Shao-An, Young, Ming-Jer, Wang, Yi-Chang, Chen, Shu-Hui, Liu, Chia-Yu, Lo, Yao-An, Jen, Hung-Hsiang, Hsu, Kai-Cheng, Hung, Jan-Jong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408266/
https://www.ncbi.nlm.nih.gov/pubmed/33846536
http://dx.doi.org/10.1038/s41418-021-00778-z
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author Wang, Shao-An
Young, Ming-Jer
Wang, Yi-Chang
Chen, Shu-Hui
Liu, Chia-Yu
Lo, Yao-An
Jen, Hung-Hsiang
Hsu, Kai-Cheng
Hung, Jan-Jong
author_facet Wang, Shao-An
Young, Ming-Jer
Wang, Yi-Chang
Chen, Shu-Hui
Liu, Chia-Yu
Lo, Yao-An
Jen, Hung-Hsiang
Hsu, Kai-Cheng
Hung, Jan-Jong
author_sort Wang, Shao-An
collection PubMed
description 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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spelling pubmed-84082662021-09-22 USP24 promotes drug resistance during cancer therapy Wang, Shao-An Young, Ming-Jer Wang, Yi-Chang Chen, Shu-Hui Liu, Chia-Yu Lo, Yao-An Jen, Hung-Hsiang Hsu, Kai-Cheng Hung, Jan-Jong Cell Death Differ Article 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. Nature Publishing Group UK 2021-04-12 2021-09 /pmc/articles/PMC8408266/ /pubmed/33846536 http://dx.doi.org/10.1038/s41418-021-00778-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Wang, Shao-An
Young, Ming-Jer
Wang, Yi-Chang
Chen, Shu-Hui
Liu, Chia-Yu
Lo, Yao-An
Jen, Hung-Hsiang
Hsu, Kai-Cheng
Hung, Jan-Jong
USP24 promotes drug resistance during cancer therapy
title USP24 promotes drug resistance during cancer therapy
title_full USP24 promotes drug resistance during cancer therapy
title_fullStr USP24 promotes drug resistance during cancer therapy
title_full_unstemmed USP24 promotes drug resistance during cancer therapy
title_short USP24 promotes drug resistance during cancer therapy
title_sort usp24 promotes drug resistance during cancer therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408266/
https://www.ncbi.nlm.nih.gov/pubmed/33846536
http://dx.doi.org/10.1038/s41418-021-00778-z
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