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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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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. |
format | Online Article Text |
id | pubmed-8408266 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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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