Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake

William A. Flavahan, Qiulian Wu, Masahiro Hitomi, Nasiha Rahim, Youngmi Kim, Andrew E. Sloan, Robert J. Weil, Ichiro Nakano, Jann N. Sarkaria, Brett W. Stringer, Bryan W. Day, Meizhang Li, Justin D. Lathia, Jeremy N. Rich, Anita B. Hjelmeland

Research output: Contribution to journalArticle

216 Scopus citations

Abstract

Like all cancers, brain tumors require a continuous source of energy and molecular resources for new cell production. In normal brain, glucose is an essential neuronal fuel, but the blood-brain barrier limits its delivery. We now report that nutrient restriction contributes to tumor progression by enriching for brain tumor initiating cells (BTICs) owing to preferential BTIC survival and to adaptation of non-BTICs through acquisition of BTIC features. BTICs outcompete for glucose uptake by co-opting the high affinity neuronal glucose transporter, type 3 (Glut3, SLC2A3). BTICs preferentially express Glut3, and targeting Glut3 inhibits BTIC growth and tumorigenic potential. Glut3, but not Glut1, correlates with poor survival in brain tumors and other cancers; thus, tumor initiating cells may extract nutrients with high affinity. As altered metabolism represents a cancer hallmark, metabolic reprogramming may maintain the tumor hierarchy and portend poor prognosis.

Original languageEnglish (US)
Pages (from-to)1373-1382
Number of pages10
JournalNature Neuroscience
Volume16
Issue number10
DOIs
StatePublished - Oct 1 2013

ASJC Scopus subject areas

  • Neuroscience(all)

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    Flavahan, W. A., Wu, Q., Hitomi, M., Rahim, N., Kim, Y., Sloan, A. E., Weil, R. J., Nakano, I., Sarkaria, J. N., Stringer, B. W., Day, B. W., Li, M., Lathia, J. D., Rich, J. N., & Hjelmeland, A. B. (2013). Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake. Nature Neuroscience, 16(10), 1373-1382. https://doi.org/10.1038/nn.3510