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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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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. |
format | Online Article Text |
id | pubmed-6714217 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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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