Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells

David L. Schonberg, Tyler E. Miller, Qiulian Wu, William A. Flavahan, Nupur K. Das, James S. Hale, Christopher G. Hubert, Stephen C. Mack, Awad M. Jarrar, Robert T. Karl, Ann Mari Rosager, Anne M. Nixon, Paul J. Tesar, Petra Hamerlik, Bjarne W. Kristensen, Craig Horbinski, James Connor, Paul L. Fox, Justin D. Lathia, Jeremy N. Rich

Research output: Contribution to journalArticlepeer-review

236 Scopus citations


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.

Original languageEnglish (US)
Article number2152
Pages (from-to)441-455
Number of pages15
JournalCancer Cell
Issue number4
StatePublished - Oct 12 2015

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cell Biology
  • Cancer Research


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