HSPB1 as a novel regulator of ferroptotic cancer cell death

X. Sun, Z. Ou, M. Xie, R. Kang, Y. Fan, X. Niu, H. Wang, L. Cao, D. Tang

Research output: Contribution to journalArticle

99 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5617-5625
Number of pages9
JournalOncogene
Volume34
Issue number45
DOIs
StatePublished - Mar 2 2015
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Sun, X., Ou, Z., Xie, M., Kang, R., Fan, Y., Niu, X., Wang, H., Cao, L., & Tang, D. (2015). HSPB1 as a novel regulator of ferroptotic cancer cell death. Oncogene, 34(45), 5617-5625. https://doi.org/10.1038/onc.2015.32