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

Nat Neurosci. 2013 Oct;16(10):1373-82. doi: 10.1038/nn.3510. Epub 2013 Sep 1.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport / physiology
  • Brain / metabolism*
  • Brain / pathology
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cell Survival / physiology
  • Female
  • Glucose / deficiency*
  • Glucose / metabolism*
  • Glucose Transporter Type 3 / biosynthesis*
  • Humans
  • Mice
  • Mice, Nude
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays / methods


  • Glucose Transporter Type 3
  • SLC2A3 protein, human
  • Glucose