Cargando…
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),...
Autores principales: | , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1785074002422661120 |
---|---|
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. |
format | Online Article Text |
id | pubmed-10349816 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT liangyiran hspb1facilitateschemoresistancethroughinhibitingferroptoticcancercelldeathandregulatingnfkbsignalingpathwayinbreastcancer AT wangyajie hspb1facilitateschemoresistancethroughinhibitingferroptoticcancercelldeathandregulatingnfkbsignalingpathwayinbreastcancer AT zhangyan hspb1facilitateschemoresistancethroughinhibitingferroptoticcancercelldeathandregulatingnfkbsignalingpathwayinbreastcancer AT yefangzhou hspb1facilitateschemoresistancethroughinhibitingferroptoticcancercelldeathandregulatingnfkbsignalingpathwayinbreastcancer AT luodan hspb1facilitateschemoresistancethroughinhibitingferroptoticcancercelldeathandregulatingnfkbsignalingpathwayinbreastcancer AT liyaming hspb1facilitateschemoresistancethroughinhibitingferroptoticcancercelldeathandregulatingnfkbsignalingpathwayinbreastcancer AT jinyuhan hspb1facilitateschemoresistancethroughinhibitingferroptoticcancercelldeathandregulatingnfkbsignalingpathwayinbreastcancer AT handianwen hspb1facilitateschemoresistancethroughinhibitingferroptoticcancercelldeathandregulatingnfkbsignalingpathwayinbreastcancer AT wangzekun hspb1facilitateschemoresistancethroughinhibitingferroptoticcancercelldeathandregulatingnfkbsignalingpathwayinbreastcancer AT chenbing hspb1facilitateschemoresistancethroughinhibitingferroptoticcancercelldeathandregulatingnfkbsignalingpathwayinbreastcancer AT zhaowenjing hspb1facilitateschemoresistancethroughinhibitingferroptoticcancercelldeathandregulatingnfkbsignalingpathwayinbreastcancer AT wanglijuan hspb1facilitateschemoresistancethroughinhibitingferroptoticcancercelldeathandregulatingnfkbsignalingpathwayinbreastcancer AT chenxi hspb1facilitateschemoresistancethroughinhibitingferroptoticcancercelldeathandregulatingnfkbsignalingpathwayinbreastcancer AT matingting hspb1facilitateschemoresistancethroughinhibitingferroptoticcancercelldeathandregulatingnfkbsignalingpathwayinbreastcancer AT kongxiaoli hspb1facilitateschemoresistancethroughinhibitingferroptoticcancercelldeathandregulatingnfkbsignalingpathwayinbreastcancer AT yangqifeng hspb1facilitateschemoresistancethroughinhibitingferroptoticcancercelldeathandregulatingnfkbsignalingpathwayinbreastcancer |