@article{b440396fc59244b982551cb63e3bbb2e,
title = "Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells",
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.",
author = "Schonberg, {David L.} and Miller, {Tyler E.} and Qiulian Wu and Flavahan, {William A.} and Das, {Nupur K.} and Hale, {James S.} and Hubert, {Christopher G.} and Mack, {Stephen C.} and Jarrar, {Awad M.} and Karl, {Robert T.} and Rosager, {Ann Mari} and Nixon, {Anne M.} and Tesar, {Paul J.} and Petra Hamerlik and Kristensen, {Bjarne W.} and Craig Horbinski and Connor, {James R.} and Fox, {Paul L.} and Lathia, {Justin D.} and Rich, {Jeremy N.}",
note = "Funding Information: We thank the Cleveland Clinic Microscopy and Flow Cores, Monica Venere for her thoughtful insight, Dana Napier for her histologic expertise, and James Morrow for help with PreSTIGE analysis. This work was supported by the American Brain Tumor Association (D.L.S.), The Peter and Carmen Lucia Buck Training Program in Translational Clinical Oncology (C.H.), the University of Kentucky College of Medicine Physician Scientist Program (C.H.), the James S. McDonnell Foundation (J.N.R.), the Danish Cancer Society Research Center (P.H), a CIHR Banting Fellowship (S.C.M.), an American Cancer Society Research Scholar Award (J.D.L), a Sontag Foundation Distinguished Scientist Award (J.D.L.), and National Institutes of Health grants T32 TRN508838 CWRU (D.L.S.), F30 CA183510 (T.E.M.), T32 GM007250 MSTP (T.E.M.), F32 CA189647 (C.G.H.), K08 CA155764 (C.H.), 2P20 RR020171 COBRE pilot grant (C.H.), K99/R00 CA157948 (J.D.L.), R01 NS083629 (J.D.L.), R21 CA198254 (J.D.L.), R21 CA191263 (J.D.L), P01 HL029582 (P.L.F), P01 HL076491 (P.L.F.), R01 DK083359 (P.L.F.), R01 CA154130 (J.N.R.), R01 CA169117 (J.N.R.), R01 CA171652 (J.N.R.), R01 NS087913 (J.N.R.), and R01 NS089272 (J.N.R.). P.J.T is a New York Stem Cell Foundation-Robertson Investigator. The TMA construction was supported by the Biospecimen and Tissue Procurement Shared Resource Facility of the University of Kentucky Markey Cancer Center (P30CA177558). Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",
year = "2015",
month = oct,
day = "12",
doi = "10.1016/j.ccell.2015.09.002",
language = "English (US)",
volume = "28",
pages = "441--455",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "4",
}
