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

Abstract

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.

• Authors: Yiran Liang, Yajie Wang, Yan Zhang, Fangzhou Ye, Dan Luo, Yaming Li, Yuhan Jin, Dianwen Han, Zekun Wang, Bing Chen, Wenjing Zhao, Lijuan Wang, Xi Chen, Tingting Ma, Xiaoli Kong, Qifeng Yang
• Journal: Cell death & disease (Cell Death Dis) Vol. 14 Issue 7 Pg. 434 (07 15 2023) ISSN: 2041-4889 [Electronic] England
• PMID: 37454220 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023. The Author(s).

Chemical References

• NF-kappa B
• HSP27 Heat-Shock Proteins
• HSPB1 protein, human
• Heat-Shock Proteins
• Molecular Chaperones

Topics

• Humans
• Female
• NF-kappa B (metabolism)
• Breast Neoplasms (drug therapy, genetics, metabolism)
• HSP27 Heat-Shock Proteins (genetics, metabolism)
• Drug Resistance, Neoplasm
• Signal Transduction
• Cell Death
• Triple Negative Breast Neoplasms
• Cell Line, Tumor
• Heat-Shock Proteins (genetics, metabolism)
• Molecular Chaperones (metabolism)