HSPB1 as a novel regulator of ferroptotic cancer cell death
Open accessAbstract
Ferroptosis is an iron-dependent form of non-apoptotic cell death, but its molecular mechanism remains largely unknown. Here, we demonstrate that heat shock protein beta-1 (HSPB1) is a negative regulator of ferroptotic cancer cell death. Erastin, a specific ferroptosis-inducing compound, stimulates heat shock factor 1 (HSF1)-dependent HSPB1 expression in cancer cells. Knockdown of HSF1 and HSPB1 enhances erastin-induced ferroptosis, whereas heat shock pretreatment and overexpression of HSPB1 inhibits erastin-induced ferroptosis. Protein kinase C-mediated HSPB1 phosphorylation confers protection against ferroptosis by reducing iron-mediated production of lipid reactive oxygen species. Moreover, inhibition of the HSF1-HSPB1 pathway and HSPB1 phosphorylation increases the anticancer activity of erastin in human xenograft mouse tumor models. Our findings reveal an essential role for HSPB1 in iron metabolism with important effects on ferroptosis-mediated cancer therapy.
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HSPB1 suppresses ferroptosis by an unknown mechanism, suggesting heat shock proteins may influence ferroptosis sensitivity in some cell contexts.
“Finally, heat shock protein beta 1 (HSPB1) was reported to suppress ferroptosis through an unknown mechanism [41]; this suggests that heat shock proteins may be important in setting the sensitivity to ferroptosis in some cell contexts.”
From Ferroptosis: Death by Lipid Peroxidation (2016) · cites this paper as [41]
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Self-citation
- Authors
- Sun, X., Ou, Z., Xie, M., Kang, R., Fan, Y., Niu, X., Wang, H., Cao, L., & Tang, D.
- Affiliations
- Third Affiliated Hospital of Guangzhou Medical University (CN)
- Central South University (CN)
- University of Pittsburgh (US)
- Feinstein Institute for Medical Research (US)
- Corresponding author
- Sun, X
- Tang, D
- Venue
- Oncogene
- Published
- 2015-03-02
- Volume
- 34
- Issue
- 45
- Pages
- 5617-5625
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- PMC
- PMC4640181
- OpenAlex
- W2100671540
- Cited by
- 666
- References
- 45
- Citations by year
- 2026: 46 · 2025: 75 · 2024: 92 · 2023: 118 · 2022: 101 · 2021: 92 · 2020: 54 · 2019: 30 · 2018: 19 · 2017: 19 · 2016: 13 · 2015: 7
- FWCI
- 15.18
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (R01CA160417)
- National Institute of General Medical Sciences (R01GM063075)
- National Center for Complementary and Integrative Health (R01AT005076)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- HSPB1, ferroptosis, heat shock factor 1, erastin, cancer cell death, protein kinase C, lipid reactive oxygen species, iron metabolism, heat shock response, chemoresistance, tumor xenografts
- MeSH terms
- Heat Shock Transcription Factors, Animals, DNA-Binding Proteins, Heat-Shock Proteins, HeLa Cells, Humans, Iron, Neoplasm Proteins, Neoplasms, Experimental, Phosphorylation, Piperazines, Transcription Factors, Mice, SCID, Mice, Inbred NOD, Cell Death, Reactive Oxygen Species, Molecular Chaperones, Heat-Shock Response, Xenograft Model Antitumor Assays, Mice, HSP27 Heat-Shock Proteins
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