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Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake.
- 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.
- Subjects :
- Animals
Biological Transport physiology
Brain pathology
Brain Neoplasms pathology
Cell Survival physiology
Female
Humans
Mice
Mice, Nude
Neoplastic Stem Cells pathology
Tumor Cells, Cultured
Xenograft Model Antitumor Assays methods
Brain metabolism
Brain Neoplasms metabolism
Glucose deficiency
Glucose metabolism
Glucose Transporter Type 3 biosynthesis
Neoplastic Stem Cells metabolism
Subjects
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