Cargando…
Aspirin attenuates YAP and β-catenin expression by promoting β-TrCP to overcome docetaxel and vinorelbine resistance in triple-negative breast cancer
The use of aspirin has been associated with reduced breast cancer risk, but it is litter known if aspirin overcomes chemoresistance in triple-negative breast cancer (TNBC). Herein, we demonstrated that changes in the expression of Yes-associated protein (YAP) and β-catenin might be a promising predi...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359325/ https://www.ncbi.nlm.nih.gov/pubmed/32661222 http://dx.doi.org/10.1038/s41419-020-2719-2 |
_version_ | 1783559025586077696 |
---|---|
author | Ma, Ji Fan, Zhenhai Tang, Qiulin Xia, Hongwei Zhang, Tao Bi, Feng |
author_facet | Ma, Ji Fan, Zhenhai Tang, Qiulin Xia, Hongwei Zhang, Tao Bi, Feng |
author_sort | Ma, Ji |
collection | PubMed |
description | The use of aspirin has been associated with reduced breast cancer risk, but it is litter known if aspirin overcomes chemoresistance in triple-negative breast cancer (TNBC). Herein, we demonstrated that changes in the expression of Yes-associated protein (YAP) and β-catenin might be a promising predictive biomarker for neoadjuvant chemotherapy sensitivity in TNBC patients. Inhibition of YAP or β-catenin enhanced the cytotoxicity of the anti-microtubule agents docetaxel and vinorelbine against drug-resistant TNBC cells as well as the sensitivity of these cells to the agents in vitro and in vivo. Interestingly, aspirin not only significantly inhibited the growth of TNBC cells, but also attenuated YAP and β-catenin expression by upregulating the E3 ubiquitin ligase β-TrCP to abolished docetaxel and vinorelbine resistance. The combination of aspirin and docetaxel or vinorelbine remarkably inhibited the growth of drug-resistant TNBC cells in vitro and in vivo. Moreover, TNBC patients with high YAP and/or β-catenin expression had a higher risk of relapse or mortality than patients with low YAP and/or β-catenin expression. Collectively, our study discovered a novel role of aspirin based on its anticancer effect, and put forward some possible mechanisms of chemoresistance in TNBC. The combined use of aspirin and anti-microtubule drugs presented several promising therapeutic approaches for TNBC treatment. |
format | Online Article Text |
id | pubmed-7359325 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-73593252020-07-20 Aspirin attenuates YAP and β-catenin expression by promoting β-TrCP to overcome docetaxel and vinorelbine resistance in triple-negative breast cancer Ma, Ji Fan, Zhenhai Tang, Qiulin Xia, Hongwei Zhang, Tao Bi, Feng Cell Death Dis Article The use of aspirin has been associated with reduced breast cancer risk, but it is litter known if aspirin overcomes chemoresistance in triple-negative breast cancer (TNBC). Herein, we demonstrated that changes in the expression of Yes-associated protein (YAP) and β-catenin might be a promising predictive biomarker for neoadjuvant chemotherapy sensitivity in TNBC patients. Inhibition of YAP or β-catenin enhanced the cytotoxicity of the anti-microtubule agents docetaxel and vinorelbine against drug-resistant TNBC cells as well as the sensitivity of these cells to the agents in vitro and in vivo. Interestingly, aspirin not only significantly inhibited the growth of TNBC cells, but also attenuated YAP and β-catenin expression by upregulating the E3 ubiquitin ligase β-TrCP to abolished docetaxel and vinorelbine resistance. The combination of aspirin and docetaxel or vinorelbine remarkably inhibited the growth of drug-resistant TNBC cells in vitro and in vivo. Moreover, TNBC patients with high YAP and/or β-catenin expression had a higher risk of relapse or mortality than patients with low YAP and/or β-catenin expression. Collectively, our study discovered a novel role of aspirin based on its anticancer effect, and put forward some possible mechanisms of chemoresistance in TNBC. The combined use of aspirin and anti-microtubule drugs presented several promising therapeutic approaches for TNBC treatment. Nature Publishing Group UK 2020-07-13 /pmc/articles/PMC7359325/ /pubmed/32661222 http://dx.doi.org/10.1038/s41419-020-2719-2 Text en © The Author(s) 2020 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/. |
spellingShingle | Article Ma, Ji Fan, Zhenhai Tang, Qiulin Xia, Hongwei Zhang, Tao Bi, Feng Aspirin attenuates YAP and β-catenin expression by promoting β-TrCP to overcome docetaxel and vinorelbine resistance in triple-negative breast cancer |
title | Aspirin attenuates YAP and β-catenin expression by promoting β-TrCP to overcome docetaxel and vinorelbine resistance in triple-negative breast cancer |
title_full | Aspirin attenuates YAP and β-catenin expression by promoting β-TrCP to overcome docetaxel and vinorelbine resistance in triple-negative breast cancer |
title_fullStr | Aspirin attenuates YAP and β-catenin expression by promoting β-TrCP to overcome docetaxel and vinorelbine resistance in triple-negative breast cancer |
title_full_unstemmed | Aspirin attenuates YAP and β-catenin expression by promoting β-TrCP to overcome docetaxel and vinorelbine resistance in triple-negative breast cancer |
title_short | Aspirin attenuates YAP and β-catenin expression by promoting β-TrCP to overcome docetaxel and vinorelbine resistance in triple-negative breast cancer |
title_sort | aspirin attenuates yap and β-catenin expression by promoting β-trcp to overcome docetaxel and vinorelbine resistance in triple-negative breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359325/ https://www.ncbi.nlm.nih.gov/pubmed/32661222 http://dx.doi.org/10.1038/s41419-020-2719-2 |
work_keys_str_mv | AT maji aspirinattenuatesyapandbcateninexpressionbypromotingbtrcptoovercomedocetaxelandvinorelbineresistanceintriplenegativebreastcancer AT fanzhenhai aspirinattenuatesyapandbcateninexpressionbypromotingbtrcptoovercomedocetaxelandvinorelbineresistanceintriplenegativebreastcancer AT tangqiulin aspirinattenuatesyapandbcateninexpressionbypromotingbtrcptoovercomedocetaxelandvinorelbineresistanceintriplenegativebreastcancer AT xiahongwei aspirinattenuatesyapandbcateninexpressionbypromotingbtrcptoovercomedocetaxelandvinorelbineresistanceintriplenegativebreastcancer AT zhangtao aspirinattenuatesyapandbcateninexpressionbypromotingbtrcptoovercomedocetaxelandvinorelbineresistanceintriplenegativebreastcancer AT bifeng aspirinattenuatesyapandbcateninexpressionbypromotingbtrcptoovercomedocetaxelandvinorelbineresistanceintriplenegativebreastcancer |