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Cytoplasmic SIRT1 inhibits cell migration and invasion by impeding epithelial–mesenchymal transition in ovarian carcinoma
Sirtuin1 (SIRT1) is a mammalian NAD(+)-dependent type III deacetylase that plays paramount roles in diverse cellular processes. The nucleocytoplasmic shuttling of SIRT1 was discovered more than a decade ago, but the roles of subcellular SIRT1 localization in tumor progression remain unclear. Here, w...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679836/ https://www.ncbi.nlm.nih.gov/pubmed/31317367 http://dx.doi.org/10.1007/s11010-019-03559-y |
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author | Yang, Tong Zhou, Ru Yu, Shentong Yu, Shuhong Cui, Zhuqing Hu, Peizhen Liu, Jinsong Qiao, Qing Zhang, Jing |
author_facet | Yang, Tong Zhou, Ru Yu, Shentong Yu, Shuhong Cui, Zhuqing Hu, Peizhen Liu, Jinsong Qiao, Qing Zhang, Jing |
author_sort | Yang, Tong |
collection | PubMed |
description | Sirtuin1 (SIRT1) is a mammalian NAD(+)-dependent type III deacetylase that plays paramount roles in diverse cellular processes. The nucleocytoplasmic shuttling of SIRT1 was discovered more than a decade ago, but the roles of subcellular SIRT1 localization in tumor progression remain unclear. Here, we report that cytoplasmic SIRT1 acts as a tumor suppressor in ovarian carcinoma. By creating ovarian carcinoma cell lines overexpressing wild-type SIRT1 and nuclear localization signals (NLSs) mutated SIRT1 together with both unbiased proteomic and acetylomic approaches and Transwell assays, we identified that mutations in the NLS sequences prevented SIRT1 from entering the nucleus, resulting in the predominant cytoplasmic localization of SIRT1; the cytoplasmic localization of SIRT1 suppressed the mesenchymal program, activated the epithelial program, and inhibited the migration and invasion of tumor cells, thus providing experimental evidence that SIRT1 functions as a tumor suppressor or oncogene may depend on its subcellular localization. Altogether, our findings may highlight a novel role of cytoplasmic SIRT1 in ovarian carcinoma, providing new possible insights for studies investigating the role of SIRT1 in tumor progression. |
format | Online Article Text |
id | pubmed-6679836 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-66798362019-08-16 Cytoplasmic SIRT1 inhibits cell migration and invasion by impeding epithelial–mesenchymal transition in ovarian carcinoma Yang, Tong Zhou, Ru Yu, Shentong Yu, Shuhong Cui, Zhuqing Hu, Peizhen Liu, Jinsong Qiao, Qing Zhang, Jing Mol Cell Biochem Article Sirtuin1 (SIRT1) is a mammalian NAD(+)-dependent type III deacetylase that plays paramount roles in diverse cellular processes. The nucleocytoplasmic shuttling of SIRT1 was discovered more than a decade ago, but the roles of subcellular SIRT1 localization in tumor progression remain unclear. Here, we report that cytoplasmic SIRT1 acts as a tumor suppressor in ovarian carcinoma. By creating ovarian carcinoma cell lines overexpressing wild-type SIRT1 and nuclear localization signals (NLSs) mutated SIRT1 together with both unbiased proteomic and acetylomic approaches and Transwell assays, we identified that mutations in the NLS sequences prevented SIRT1 from entering the nucleus, resulting in the predominant cytoplasmic localization of SIRT1; the cytoplasmic localization of SIRT1 suppressed the mesenchymal program, activated the epithelial program, and inhibited the migration and invasion of tumor cells, thus providing experimental evidence that SIRT1 functions as a tumor suppressor or oncogene may depend on its subcellular localization. Altogether, our findings may highlight a novel role of cytoplasmic SIRT1 in ovarian carcinoma, providing new possible insights for studies investigating the role of SIRT1 in tumor progression. Springer US 2019-07-17 2019 /pmc/articles/PMC6679836/ /pubmed/31317367 http://dx.doi.org/10.1007/s11010-019-03559-y Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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. |
spellingShingle | Article Yang, Tong Zhou, Ru Yu, Shentong Yu, Shuhong Cui, Zhuqing Hu, Peizhen Liu, Jinsong Qiao, Qing Zhang, Jing Cytoplasmic SIRT1 inhibits cell migration and invasion by impeding epithelial–mesenchymal transition in ovarian carcinoma |
title | Cytoplasmic SIRT1 inhibits cell migration and invasion by impeding epithelial–mesenchymal transition in ovarian carcinoma |
title_full | Cytoplasmic SIRT1 inhibits cell migration and invasion by impeding epithelial–mesenchymal transition in ovarian carcinoma |
title_fullStr | Cytoplasmic SIRT1 inhibits cell migration and invasion by impeding epithelial–mesenchymal transition in ovarian carcinoma |
title_full_unstemmed | Cytoplasmic SIRT1 inhibits cell migration and invasion by impeding epithelial–mesenchymal transition in ovarian carcinoma |
title_short | Cytoplasmic SIRT1 inhibits cell migration and invasion by impeding epithelial–mesenchymal transition in ovarian carcinoma |
title_sort | cytoplasmic sirt1 inhibits cell migration and invasion by impeding epithelial–mesenchymal transition in ovarian carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679836/ https://www.ncbi.nlm.nih.gov/pubmed/31317367 http://dx.doi.org/10.1007/s11010-019-03559-y |
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