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

74 Citations (Scopus)

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

Fingerprint

HSP27 Heat-Shock Proteins
Cell Death
Shock
Neoplasms
Hot Temperature
Iron
Phosphorylation
Heterografts
Protein Kinase C
Reactive Oxygen Species
Lipids
erastin

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

HSPB1 as a novel regulator of ferroptotic cancer cell death. / Sun, X.; Ou, Z.; Xie, M.; Kang, R.; Fan, Y.; Niu, X.; Wang, H.; Cao, L.; Tang, D.

In: Oncogene, Vol. 34, No. 45, 02.03.2015, p. 5617-5625.

Research output: Contribution to journalArticle

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, vol. 34, no. 45, pp. 5617-5625. https://doi.org/10.1038/onc.2015.32
Sun, X. ; Ou, Z. ; Xie, M. ; Kang, R. ; Fan, Y. ; Niu, X. ; Wang, H. ; Cao, L. ; Tang, D. / HSPB1 as a novel regulator of ferroptotic cancer cell death. In: Oncogene. 2015 ; Vol. 34, No. 45. pp. 5617-5625.
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AU - Niu, X.

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AU - Cao, L.

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