期刊
CANCER CELL
卷 28, 期 4, 页码 441-455出版社
CELL PRESS
DOI: 10.1016/j.ccell.2015.09.002
关键词
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资金
- American Brain Tumor Association
- Peter and Carmen Lucia Buck Training Program in Translational Clinical Oncology
- University of Kentucky College of Medicine
- James S. McDonnell Foundation
- Danish Cancer Society Research Center
- CIHR
- American Cancer Society
- Sontag Foundation
- National Institutes of Health [T32 TRN508838 CWRU, F30 CA183510, T32 GM007250 MSTP, F32 CA189647, K08 CA155764, 2P20 RR020171 COBRE, K99/R00 CA157948]
- Biospecimen and Tissue Procurement Shared Resource Facility of the University of Kentucky Markey Cancer Center [P30CA177558]
- The National Institutes of Health [R01 NS083629, R21 CA198254, R21 CA191263, P01 HL029582, P01 HL076491, R01 DK083359, R01 CA154130, R01 CA169117, R01 CA171652, R01 NS087913, R01 NS089272]
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.
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