Details
- Autor(en) / Beteiligte
- Titel
- HSPB1 as a novel regulator of ferroptotic cancer cell death
- Ist Teil von
- Oncogene, 2015-11, Vol.34 (45), p.5617-5625
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2015
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0950-9232eISSN: 1476-5594DOI: 10.1038/onc.2015.32Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4640181
- Format
- –
- Schlagworte
- Analysis, Animal models, Animals, Antitumor activity, Apoptosis, Biochemistry, Cancer, Care and treatment, Cell Death, Complications and side effects, DNA-Binding Proteins - genetics, DNA-Binding Proteins - metabolism, Ferroptosis, Heat shock factors, Heat shock proteins, Heat Shock Transcription Factors, Heat-Shock Response - drug effects, Heat-Shock Response - genetics, HeLa Cells, HSF1 protein, HSP27 Heat-Shock Proteins - genetics, HSP27 Heat-Shock Proteins - metabolism, Humans, Influence, Iron, Iron - metabolism, Kinases, Mice, Mice, Inbred NOD, Mice, SCID, Neoplasm Proteins - genetics, Neoplasm Proteins - metabolism, Neoplasms, Experimental - drug therapy, Neoplasms, Experimental - genetics, Neoplasms, Experimental - metabolism, Neoplasms, Experimental - pathology, Phosphorylation, Phosphorylation - drug effects, Phosphorylation - genetics, Piperazines - pharmacology, Protein kinase C, Reactive oxygen species, Reactive Oxygen Species - metabolism, Transcription Factors - genetics, Transcription Factors - metabolism, Xenograft Model Antitumor Assays, Xenografts