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PLK1 and AURKB phosphorylate survivin differentially to affect proliferation in racially distinct triple-negative breast cancer
Protein diversity due to alternative mRNA splicing or post-translational modifications (PTMs) plays a vital role in various cellular functions. The mitotic kinases polo-like kinase 1 (PLK1) and Aurora B (AURKB) phosphorylate survivin, an inhibitor of apoptosis (IAP) family member, thereby regulating...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9832024/ https://www.ncbi.nlm.nih.gov/pubmed/36627281 http://dx.doi.org/10.1038/s41419-022-05539-5 |
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author | Garlapati, Chakravarthy Joshi, Shriya Bhattarai, Shristi Krishnamurthy, Jayashree Turaga, Ravi Chakra Nguyen, Thi Li, Xiaoxian Aneja, Ritu |
author_facet | Garlapati, Chakravarthy Joshi, Shriya Bhattarai, Shristi Krishnamurthy, Jayashree Turaga, Ravi Chakra Nguyen, Thi Li, Xiaoxian Aneja, Ritu |
author_sort | Garlapati, Chakravarthy |
collection | PubMed |
description | Protein diversity due to alternative mRNA splicing or post-translational modifications (PTMs) plays a vital role in various cellular functions. The mitotic kinases polo-like kinase 1 (PLK1) and Aurora B (AURKB) phosphorylate survivin, an inhibitor of apoptosis (IAP) family member, thereby regulating cell proliferation. PLK1, AURKB, and survivin are overexpressed in triple-negative breast cancer (TNBC), an aggressive breast cancer subtype. TNBC is associated with high proliferative capacity, high rates of distant metastasis, and treatment resistance. The proliferation-promoting protein survivin and its activating kinases, PLK1 and AURKB, are overexpressed in TNBC. In this study, we investigated the role of survivin phosphorylation in racial disparities in TNBC cell proliferation. Analysis of TCGA TNBC data revealed higher expression levels of PLK1 (P = 0.026) and AURKB (P = 0.045) in African Americans (AAs; n = 41) than in European Americans (EAs; n = 86). In contrast, no significant racial differences in survivin mRNA or protein levels were observed. AA TNBC cells exhibited higher p-survivin levels than EA TNBC cells. Survivin silencing using small interfering RNAs significantly attenuated cell proliferation and cell cycle progression in AA TNBC cells, but not in EA TNBC cells. In addition, PLK1 and AURKB inhibition with volasertib and barasertib significantly inhibited the growth of AA TNBC xenografts, but not of EA TNBC tumors. These data suggest that inhibition of PLK1 and AURKB suppresses cell proliferation and tumor growth, specifically in AA TNBC. These findings suggest that targeting survivin phosphorylation may be a viable therapeutic option for AA patients with TNBC. [Image: see text] |
format | Online Article Text |
id | pubmed-9832024 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-98320242023-01-12 PLK1 and AURKB phosphorylate survivin differentially to affect proliferation in racially distinct triple-negative breast cancer Garlapati, Chakravarthy Joshi, Shriya Bhattarai, Shristi Krishnamurthy, Jayashree Turaga, Ravi Chakra Nguyen, Thi Li, Xiaoxian Aneja, Ritu Cell Death Dis Article Protein diversity due to alternative mRNA splicing or post-translational modifications (PTMs) plays a vital role in various cellular functions. The mitotic kinases polo-like kinase 1 (PLK1) and Aurora B (AURKB) phosphorylate survivin, an inhibitor of apoptosis (IAP) family member, thereby regulating cell proliferation. PLK1, AURKB, and survivin are overexpressed in triple-negative breast cancer (TNBC), an aggressive breast cancer subtype. TNBC is associated with high proliferative capacity, high rates of distant metastasis, and treatment resistance. The proliferation-promoting protein survivin and its activating kinases, PLK1 and AURKB, are overexpressed in TNBC. In this study, we investigated the role of survivin phosphorylation in racial disparities in TNBC cell proliferation. Analysis of TCGA TNBC data revealed higher expression levels of PLK1 (P = 0.026) and AURKB (P = 0.045) in African Americans (AAs; n = 41) than in European Americans (EAs; n = 86). In contrast, no significant racial differences in survivin mRNA or protein levels were observed. AA TNBC cells exhibited higher p-survivin levels than EA TNBC cells. Survivin silencing using small interfering RNAs significantly attenuated cell proliferation and cell cycle progression in AA TNBC cells, but not in EA TNBC cells. In addition, PLK1 and AURKB inhibition with volasertib and barasertib significantly inhibited the growth of AA TNBC xenografts, but not of EA TNBC tumors. These data suggest that inhibition of PLK1 and AURKB suppresses cell proliferation and tumor growth, specifically in AA TNBC. These findings suggest that targeting survivin phosphorylation may be a viable therapeutic option for AA patients with TNBC. [Image: see text] Nature Publishing Group UK 2023-01-10 /pmc/articles/PMC9832024/ /pubmed/36627281 http://dx.doi.org/10.1038/s41419-022-05539-5 Text en © The Author(s) 2023 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 Garlapati, Chakravarthy Joshi, Shriya Bhattarai, Shristi Krishnamurthy, Jayashree Turaga, Ravi Chakra Nguyen, Thi Li, Xiaoxian Aneja, Ritu PLK1 and AURKB phosphorylate survivin differentially to affect proliferation in racially distinct triple-negative breast cancer |
title | PLK1 and AURKB phosphorylate survivin differentially to affect proliferation in racially distinct triple-negative breast cancer |
title_full | PLK1 and AURKB phosphorylate survivin differentially to affect proliferation in racially distinct triple-negative breast cancer |
title_fullStr | PLK1 and AURKB phosphorylate survivin differentially to affect proliferation in racially distinct triple-negative breast cancer |
title_full_unstemmed | PLK1 and AURKB phosphorylate survivin differentially to affect proliferation in racially distinct triple-negative breast cancer |
title_short | PLK1 and AURKB phosphorylate survivin differentially to affect proliferation in racially distinct triple-negative breast cancer |
title_sort | plk1 and aurkb phosphorylate survivin differentially to affect proliferation in racially distinct triple-negative breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9832024/ https://www.ncbi.nlm.nih.gov/pubmed/36627281 http://dx.doi.org/10.1038/s41419-022-05539-5 |
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