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

Authors :
Flavahan WA
Wu Q
Hitomi M
Rahim N
Kim Y
Sloan AE
Weil RJ
Nakano I
Sarkaria JN
Stringer BW
Day BW
Li M
Lathia JD
Rich JN
Hjelmeland AB
Source :
Nature neuroscience [Nat Neurosci] 2013 Oct; Vol. 16 (10), pp. 1373-82. Date of Electronic Publication: 2013 Sep 01.
Publication Year :
2013

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.

Details

Language :
English
ISSN :
1546-1726
Volume :
16
Issue :
10
Database :
MEDLINE
Journal :
Nature neuroscience
Publication Type :
Academic Journal
Accession number :
23995067
Full Text :
https://doi.org/10.1038/nn.3510