| Literature DB >> 26461092 |
David L Schonberg1, Tyler E Miller1, Qiulian Wu1, William A Flavahan1, Nupur K Das2, James S Hale2, Christopher G Hubert1, Stephen C Mack1, Awad M Jarrar2, Robert T Karl3, Ann Mari Rosager4, Anne M Nixon5, Paul J Tesar3, Petra Hamerlik6, Bjarne W Kristensen4, Craig Horbinski7, James R Connor5, Paul L Fox2, Justin D Lathia2, Jeremy N Rich8.
Abstract
Glioblastomas display hierarchies with self-renewing cancer stem-like cells (CSCs). RNA sequencing and enhancer mapping revealed regulatory programs unique to CSCs causing upregulation of the iron transporter transferrin, the top differentially expressed gene compared with tissue-specific progenitors. Direct interrogation of iron uptake demonstrated that CSCs potently extract iron from the microenvironment more effectively than other tumor cells. Systematic interrogation of iron flux determined that CSCs preferentially require transferrin receptor and ferritin, two core iron regulators, to propagate and form tumors in vivo. Depleting ferritin disrupted CSC mitotic progression, through the STAT3-FoxM1 regulatory axis, revealing an iron-regulated CSC pathway. Iron is a unique, primordial metal fundamental for earliest life forms, on which CSCs have an epigenetically programmed, targetable dependence.Entities:
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Year: 2015 PMID： 26461092 PMCID： PMC4646058 DOI： 10.1016/j.ccell.2015.09.002
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743