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Aurora kinase A stabilizes FOXM1 to enhance paclitaxel resistance in triple‐negative breast cancer

Triple‐negative breast cancer (TNBC) has a relatively poor outcome. Acquired chemoresistance is a major clinical challenge for TNBC patients. Previously, we reported that kinase‐dead Aurora kinase A (Aurora‐A) could effectively transactivate the FOXM1 promoter. Here, we demonstrate an additional pat...

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Autores principales: Yang, Na, Wang, Chang, Wang, Jian, Wang, Zifeng, Huang, Di, Yan, Min, Kamran, Muhammad, Liu, Quentin, Xu, BangLao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714217/
https://www.ncbi.nlm.nih.gov/pubmed/31359594
http://dx.doi.org/10.1111/jcmm.14538
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author Yang, Na
Wang, Chang
Wang, Jian
Wang, Zifeng
Huang, Di
Yan, Min
Kamran, Muhammad
Liu, Quentin
Xu, BangLao
author_facet Yang, Na
Wang, Chang
Wang, Jian
Wang, Zifeng
Huang, Di
Yan, Min
Kamran, Muhammad
Liu, Quentin
Xu, BangLao
author_sort Yang, Na
collection PubMed
description Triple‐negative breast cancer (TNBC) has a relatively poor outcome. Acquired chemoresistance is a major clinical challenge for TNBC patients. Previously, we reported that kinase‐dead Aurora kinase A (Aurora‐A) could effectively transactivate the FOXM1 promoter. Here, we demonstrate an additional pathway through which Aurora‐A stabilizes FOXM1 by attenuating its ubiquitin in TNBC. Specifically, Aurora‐A stabilizes FOXM1 in late M phase and early G1 phase of the cell cycle, which promotes proliferation of TNBC cells. Knock‐down of Aurora‐A significantly suppresses cell proliferation in TNBC cell lines and can be rescued by FOXM1 overexpression. We observe that paclitaxel‐resistant TNBC cells exhibit high expression of Aurora‐A and FOXM1. Overexpression of Aurora‐A offers TNBC cells an additional growth advantage and protection against paclitaxel. Moreover, Aurora‐A and FOXM1 could be simultaneously targeted by thiostrepton. Combination of thiostrepton and paclitaxel treatment reverses paclitaxel resistance and significantly inhibits cell proliferation. In conclusion, our study reveals additional mechanism through which Aurora‐A regulates FOXM1 and provides a new therapeutic strategy to treat paclitaxel‐resistant triple‐negative breast cancer.
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spelling pubmed-67142172019-09-05 Aurora kinase A stabilizes FOXM1 to enhance paclitaxel resistance in triple‐negative breast cancer Yang, Na Wang, Chang Wang, Jian Wang, Zifeng Huang, Di Yan, Min Kamran, Muhammad Liu, Quentin Xu, BangLao J Cell Mol Med Original Articles Triple‐negative breast cancer (TNBC) has a relatively poor outcome. Acquired chemoresistance is a major clinical challenge for TNBC patients. Previously, we reported that kinase‐dead Aurora kinase A (Aurora‐A) could effectively transactivate the FOXM1 promoter. Here, we demonstrate an additional pathway through which Aurora‐A stabilizes FOXM1 by attenuating its ubiquitin in TNBC. Specifically, Aurora‐A stabilizes FOXM1 in late M phase and early G1 phase of the cell cycle, which promotes proliferation of TNBC cells. Knock‐down of Aurora‐A significantly suppresses cell proliferation in TNBC cell lines and can be rescued by FOXM1 overexpression. We observe that paclitaxel‐resistant TNBC cells exhibit high expression of Aurora‐A and FOXM1. Overexpression of Aurora‐A offers TNBC cells an additional growth advantage and protection against paclitaxel. Moreover, Aurora‐A and FOXM1 could be simultaneously targeted by thiostrepton. Combination of thiostrepton and paclitaxel treatment reverses paclitaxel resistance and significantly inhibits cell proliferation. In conclusion, our study reveals additional mechanism through which Aurora‐A regulates FOXM1 and provides a new therapeutic strategy to treat paclitaxel‐resistant triple‐negative breast cancer. John Wiley and Sons Inc. 2019-07-30 2019-09 /pmc/articles/PMC6714217/ /pubmed/31359594 http://dx.doi.org/10.1111/jcmm.14538 Text en © 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Yang, Na
Wang, Chang
Wang, Jian
Wang, Zifeng
Huang, Di
Yan, Min
Kamran, Muhammad
Liu, Quentin
Xu, BangLao
Aurora kinase A stabilizes FOXM1 to enhance paclitaxel resistance in triple‐negative breast cancer
title Aurora kinase A stabilizes FOXM1 to enhance paclitaxel resistance in triple‐negative breast cancer
title_full Aurora kinase A stabilizes FOXM1 to enhance paclitaxel resistance in triple‐negative breast cancer
title_fullStr Aurora kinase A stabilizes FOXM1 to enhance paclitaxel resistance in triple‐negative breast cancer
title_full_unstemmed Aurora kinase A stabilizes FOXM1 to enhance paclitaxel resistance in triple‐negative breast cancer
title_short Aurora kinase A stabilizes FOXM1 to enhance paclitaxel resistance in triple‐negative breast cancer
title_sort aurora kinase a stabilizes foxm1 to enhance paclitaxel resistance in triple‐negative breast cancer
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714217/
https://www.ncbi.nlm.nih.gov/pubmed/31359594
http://dx.doi.org/10.1111/jcmm.14538
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