Journal
ONCOGENE
Volume 34, Issue 45, Pages 5617-5625Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2015.32
Keywords
-
Funding
- National Institutes of Health [R01CA160417]
- Pancreatic Cancer Action Network-AACR Career Development Award [13-20-25-TANG]
- National Natural Science Foundation-Guangdong Joint Fund [U1132005]
- Science and Information Technology of Guangzhou Key Project [2011Y1-00038]
- National Center of Complementary and Alternative Medicine [R01AT005076]
- National Institute of General Medical Sciences [R01GM063075]
Ask authors/readers for more resources
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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available