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...

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Published in:Molecular and cellular biochemistry 2019-09, Vol.459 (1-2), p.157-169
Main Authors: Yang, Tong, Zhou, Ru, Yu, Shentong, Yu, Shuhong, Cui, Zhuqing, Hu, Peizhen, Liu, Jinsong, Qiao, Qing, Zhang, Jing
Format: Article
Language:English
Subjects:
Biochemistry
Biomedical and Life Sciences
Cancer
Carcinoma
Cardiology
Cell adhesion & migration
Cell migration
Ethylenediaminetetraacetic acid
Life Sciences
Localization
Medical Biochemistry
Mesenchyme
Mutation
NAD
Oncology
Ovarian cancer
Ovarian carcinoma
SIRT1 protein
Stem cells
Tumor cell lines
Tumor cells
Tumor suppressor genes
Tumors
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Summary: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.
ISSN:0300-8177
1573-4919
DOI:10.1007/s11010-019-03559-y