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HSPB1 facilitates chemoresistance through inhibiting ferroptotic cancer cell death and regulating NF-κB signaling pathway in breast cancer

Chemoresistance is one of the major causes of therapeutic failure and poor prognosis for breast cancer patients, especially for triple-negative breast cancer patients. However, the underlying mechanism remains elusive. Here, we identified novel functional roles of heat shock protein beta-1 (HSPB1),...

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Autores principales: Liang, Yiran, Wang, Yajie, Zhang, Yan, Ye, Fangzhou, Luo, Dan, Li, Yaming, Jin, Yuhan, Han, Dianwen, Wang, Zekun, Chen, Bing, Zhao, Wenjing, Wang, Lijuan, Chen, Xi, Ma, Tingting, Kong, Xiaoli, Yang, Qifeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10349816/
https://www.ncbi.nlm.nih.gov/pubmed/37454220
http://dx.doi.org/10.1038/s41419-023-05972-0
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author Liang, Yiran
Wang, Yajie
Zhang, Yan
Ye, Fangzhou
Luo, Dan
Li, Yaming
Jin, Yuhan
Han, Dianwen
Wang, Zekun
Chen, Bing
Zhao, Wenjing
Wang, Lijuan
Chen, Xi
Ma, Tingting
Kong, Xiaoli
Yang, Qifeng
author_facet Liang, Yiran
Wang, Yajie
Zhang, Yan
Ye, Fangzhou
Luo, Dan
Li, Yaming
Jin, Yuhan
Han, Dianwen
Wang, Zekun
Chen, Bing
Zhao, Wenjing
Wang, Lijuan
Chen, Xi
Ma, Tingting
Kong, Xiaoli
Yang, Qifeng
author_sort Liang, Yiran
collection PubMed
description Chemoresistance is one of the major causes of therapeutic failure and poor prognosis for breast cancer patients, especially for triple-negative breast cancer patients. However, the underlying mechanism remains elusive. Here, we identified novel functional roles of heat shock protein beta-1 (HSPB1), regulating chemoresistance and ferroptotic cell death in breast cancer. Based on TCGA and GEO databases, HSPB1 expression was upregulated in breast cancer tissues and associated with poor prognosis of breast cancer patients, which was considered an independent prognostic factor for breast cancer. Functional assays revealed that HSPB1 could promote cancer growth and metastasis in vitro and in vivo. Furthermore, HSPB1 facilitated doxorubicin (DOX) resistance through protecting breast cancer cells from drug-induced ferroptosis. Mechanistically, HSPB1 could bind with Ikβ-α and promote its ubiquitination-mediated degradation, leading to increased nuclear translocation and activation of NF-κB signaling. In addition, HSPB1 overexpression led to enhanced secretion of IL6, which further facilitated breast cancer progression. These findings revealed that HSPB1 upregulation might be a key driver to progression and chemoresistance through regulating ferroptosis in breast cancer while targeting HSPB1 could be an effective strategy against breast cancer.
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spelling pubmed-103498162023-07-17 HSPB1 facilitates chemoresistance through inhibiting ferroptotic cancer cell death and regulating NF-κB signaling pathway in breast cancer Liang, Yiran Wang, Yajie Zhang, Yan Ye, Fangzhou Luo, Dan Li, Yaming Jin, Yuhan Han, Dianwen Wang, Zekun Chen, Bing Zhao, Wenjing Wang, Lijuan Chen, Xi Ma, Tingting Kong, Xiaoli Yang, Qifeng Cell Death Dis Article Chemoresistance is one of the major causes of therapeutic failure and poor prognosis for breast cancer patients, especially for triple-negative breast cancer patients. However, the underlying mechanism remains elusive. Here, we identified novel functional roles of heat shock protein beta-1 (HSPB1), regulating chemoresistance and ferroptotic cell death in breast cancer. Based on TCGA and GEO databases, HSPB1 expression was upregulated in breast cancer tissues and associated with poor prognosis of breast cancer patients, which was considered an independent prognostic factor for breast cancer. Functional assays revealed that HSPB1 could promote cancer growth and metastasis in vitro and in vivo. Furthermore, HSPB1 facilitated doxorubicin (DOX) resistance through protecting breast cancer cells from drug-induced ferroptosis. Mechanistically, HSPB1 could bind with Ikβ-α and promote its ubiquitination-mediated degradation, leading to increased nuclear translocation and activation of NF-κB signaling. In addition, HSPB1 overexpression led to enhanced secretion of IL6, which further facilitated breast cancer progression. These findings revealed that HSPB1 upregulation might be a key driver to progression and chemoresistance through regulating ferroptosis in breast cancer while targeting HSPB1 could be an effective strategy against breast cancer. Nature Publishing Group UK 2023-07-15 /pmc/articles/PMC10349816/ /pubmed/37454220 http://dx.doi.org/10.1038/s41419-023-05972-0 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
Liang, Yiran
Wang, Yajie
Zhang, Yan
Ye, Fangzhou
Luo, Dan
Li, Yaming
Jin, Yuhan
Han, Dianwen
Wang, Zekun
Chen, Bing
Zhao, Wenjing
Wang, Lijuan
Chen, Xi
Ma, Tingting
Kong, Xiaoli
Yang, Qifeng
HSPB1 facilitates chemoresistance through inhibiting ferroptotic cancer cell death and regulating NF-κB signaling pathway in breast cancer
title HSPB1 facilitates chemoresistance through inhibiting ferroptotic cancer cell death and regulating NF-κB signaling pathway in breast cancer
title_full HSPB1 facilitates chemoresistance through inhibiting ferroptotic cancer cell death and regulating NF-κB signaling pathway in breast cancer
title_fullStr HSPB1 facilitates chemoresistance through inhibiting ferroptotic cancer cell death and regulating NF-κB signaling pathway in breast cancer
title_full_unstemmed HSPB1 facilitates chemoresistance through inhibiting ferroptotic cancer cell death and regulating NF-κB signaling pathway in breast cancer
title_short HSPB1 facilitates chemoresistance through inhibiting ferroptotic cancer cell death and regulating NF-κB signaling pathway in breast cancer
title_sort hspb1 facilitates chemoresistance through inhibiting ferroptotic cancer cell death and regulating nf-κb signaling pathway in breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10349816/
https://www.ncbi.nlm.nih.gov/pubmed/37454220
http://dx.doi.org/10.1038/s41419-023-05972-0
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