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SRPK1 acetylation modulates alternative splicing to regulate cisplatin resistance in breast cancer cells

Cisplatin and other platinum-based compounds are frequently used to treat breast cancer, but their utility is severely compromised by drug resistance. Many genes dictating drug responsiveness are subject to pre-mRNA alternative splicing which is regulated by key kinases such as the serine-arginine p...

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Autores principales: Wang, Cheng, Zhou, Zhihong, Subhramanyam, Charannya Sozheesvari, Cao, Qiong, Heng, Zealyn Shi Lin, Liu, Wen, Fu, Xiangdong, Hu, Qidong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253463/
https://www.ncbi.nlm.nih.gov/pubmed/32461560
http://dx.doi.org/10.1038/s42003-020-0983-4
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author Wang, Cheng
Zhou, Zhihong
Subhramanyam, Charannya Sozheesvari
Cao, Qiong
Heng, Zealyn Shi Lin
Liu, Wen
Fu, Xiangdong
Hu, Qidong
author_facet Wang, Cheng
Zhou, Zhihong
Subhramanyam, Charannya Sozheesvari
Cao, Qiong
Heng, Zealyn Shi Lin
Liu, Wen
Fu, Xiangdong
Hu, Qidong
author_sort Wang, Cheng
collection PubMed
description Cisplatin and other platinum-based compounds are frequently used to treat breast cancer, but their utility is severely compromised by drug resistance. Many genes dictating drug responsiveness are subject to pre-mRNA alternative splicing which is regulated by key kinases such as the serine-arginine protein kinase 1 (SRPK1). However, its contribution to drug resistance remains controversial. In this study, we have identified that Tip60-mediated acetylation of SRPK1 is closely associated with chemotherapy sensitivity. In breast cancer cells, cisplatin induced SRPK1 acetylation but in the corresponding resistant cells, it reduced acetylation yet increased phosphorylation and kinase activity of SRPK1, favouring the splicing of some anti-apoptotic variants. Significantly, the cisplatin-resistant cells could be re-sensitized by enhancing SRPK1 acetylation or inhibiting its kinase activity. Hence, our study reveals a key role of SRPK1 in the development of cisplatin resistance in breast cancer cells and suggests a potential therapeutic avenue for overcoming chemotherapy resistance.
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spelling pubmed-72534632020-06-10 SRPK1 acetylation modulates alternative splicing to regulate cisplatin resistance in breast cancer cells Wang, Cheng Zhou, Zhihong Subhramanyam, Charannya Sozheesvari Cao, Qiong Heng, Zealyn Shi Lin Liu, Wen Fu, Xiangdong Hu, Qidong Commun Biol Article Cisplatin and other platinum-based compounds are frequently used to treat breast cancer, but their utility is severely compromised by drug resistance. Many genes dictating drug responsiveness are subject to pre-mRNA alternative splicing which is regulated by key kinases such as the serine-arginine protein kinase 1 (SRPK1). However, its contribution to drug resistance remains controversial. In this study, we have identified that Tip60-mediated acetylation of SRPK1 is closely associated with chemotherapy sensitivity. In breast cancer cells, cisplatin induced SRPK1 acetylation but in the corresponding resistant cells, it reduced acetylation yet increased phosphorylation and kinase activity of SRPK1, favouring the splicing of some anti-apoptotic variants. Significantly, the cisplatin-resistant cells could be re-sensitized by enhancing SRPK1 acetylation or inhibiting its kinase activity. Hence, our study reveals a key role of SRPK1 in the development of cisplatin resistance in breast cancer cells and suggests a potential therapeutic avenue for overcoming chemotherapy resistance. Nature Publishing Group UK 2020-05-27 /pmc/articles/PMC7253463/ /pubmed/32461560 http://dx.doi.org/10.1038/s42003-020-0983-4 Text en © The Author(s) 2020 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/.
spellingShingle Article
Wang, Cheng
Zhou, Zhihong
Subhramanyam, Charannya Sozheesvari
Cao, Qiong
Heng, Zealyn Shi Lin
Liu, Wen
Fu, Xiangdong
Hu, Qidong
SRPK1 acetylation modulates alternative splicing to regulate cisplatin resistance in breast cancer cells
title SRPK1 acetylation modulates alternative splicing to regulate cisplatin resistance in breast cancer cells
title_full SRPK1 acetylation modulates alternative splicing to regulate cisplatin resistance in breast cancer cells
title_fullStr SRPK1 acetylation modulates alternative splicing to regulate cisplatin resistance in breast cancer cells
title_full_unstemmed SRPK1 acetylation modulates alternative splicing to regulate cisplatin resistance in breast cancer cells
title_short SRPK1 acetylation modulates alternative splicing to regulate cisplatin resistance in breast cancer cells
title_sort srpk1 acetylation modulates alternative splicing to regulate cisplatin resistance in breast cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253463/
https://www.ncbi.nlm.nih.gov/pubmed/32461560
http://dx.doi.org/10.1038/s42003-020-0983-4
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