HSPB1 as a novel regulator of ferroptotic cancer cell death.

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.
Authors	X Sun, Z Ou, M Xie, R Kang, Y Fan, X Niu, H Wang, L Cao, D Tang
Journal	Oncogene (Oncogene) Vol. 34 Issue 45 Pg. 5617-25 (Nov 05 2015) ISSN: 1476-5594 [Electronic] England
PMID	25728673 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	DNA-Binding Proteins HSF1 protein, human HSP27 Heat-Shock Proteins HSPB1 protein, human Heat Shock Transcription Factors Heat-Shock Proteins Molecular Chaperones Neoplasm Proteins Piperazines Reactive Oxygen Species Transcription Factors erastin Iron
Topics	Animals Cell Death DNA-Binding Proteins (genetics, metabolism) HSP27 Heat-Shock Proteins (genetics, metabolism) HeLa Cells Heat Shock Transcription Factors Heat-Shock Proteins Heat-Shock Response (drug effects, genetics) Humans Iron (metabolism) Mice Mice, Inbred NOD Mice, SCID Molecular Chaperones Neoplasm Proteins (genetics, metabolism) Neoplasms, Experimental (drug therapy, genetics, metabolism, pathology) Phosphorylation (drug effects, genetics) Piperazines (pharmacology) Reactive Oxygen Species (metabolism) Transcription Factors (genetics, metabolism) Xenograft Model Antitumor Assays

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