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Purine synthesis promotes maintenance of brain tumor initiating cells in glioma.

Publication ,  Journal Article
Wang, X; Yang, K; Xie, Q; Wu, Q; Mack, SC; Shi, Y; Kim, LJY; Prager, BC; Flavahan, WA; Liu, X; Singer, M; Hubert, CG; Miller, TE; Zhou, W ...
Published in: Nature neuroscience
May 2017

Brain tumor initiating cells (BTICs), also known as cancer stem cells, hijack high-affinity glucose uptake active normally in neurons to maintain energy demands. Here we link metabolic dysregulation in human BTICs to a nexus between MYC and de novo purine synthesis, mediating glucose-sustained anabolic metabolism. Inhibiting purine synthesis abrogated BTIC growth, self-renewal and in vivo tumor formation by depleting intracellular pools of purine nucleotides, supporting purine synthesis as a potential therapeutic point of fragility. In contrast, differentiated glioma cells were unaffected by the targeting of purine biosynthetic enzymes, suggesting selective dependence of BTICs. MYC coordinated the control of purine synthetic enzymes, supporting its role in metabolic reprogramming. Elevated expression of purine synthetic enzymes correlated with poor prognosis in glioblastoma patients. Collectively, our results suggest that stem-like glioma cells reprogram their metabolism to self-renew and fuel the tumor hierarchy, revealing potential BTIC cancer dependencies amenable to targeted therapy.

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Published In

Nature neuroscience

DOI

EISSN

1546-1726

ISSN

1097-6256

Publication Date

May 2017

Volume

20

Issue

5

Start / End Page

661 / 673

Related Subject Headings

  • Up-Regulation
  • Ribose-Phosphate Pyrophosphokinase
  • Purines
  • Proto-Oncogene Proteins c-myc
  • Neurology & Neurosurgery
  • Neoplastic Stem Cells
  • Metabolomics
  • Humans
  • Guanosine Monophosphate
  • Glycolysis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wang, X., Yang, K., Xie, Q., Wu, Q., Mack, S. C., Shi, Y., … Rich, J. N. (2017). Purine synthesis promotes maintenance of brain tumor initiating cells in glioma. Nature Neuroscience, 20(5), 661–673. https://doi.org/10.1038/nn.4537
Wang, Xiuxing, Kailin Yang, Qi Xie, Qiulian Wu, Stephen C. Mack, Yu Shi, Leo J. Y. Kim, et al. “Purine synthesis promotes maintenance of brain tumor initiating cells in glioma.Nature Neuroscience 20, no. 5 (May 2017): 661–73. https://doi.org/10.1038/nn.4537.
Wang X, Yang K, Xie Q, Wu Q, Mack SC, Shi Y, et al. Purine synthesis promotes maintenance of brain tumor initiating cells in glioma. Nature neuroscience. 2017 May;20(5):661–73.
Wang, Xiuxing, et al. “Purine synthesis promotes maintenance of brain tumor initiating cells in glioma.Nature Neuroscience, vol. 20, no. 5, May 2017, pp. 661–73. Epmc, doi:10.1038/nn.4537.
Wang X, Yang K, Xie Q, Wu Q, Mack SC, Shi Y, Kim LJY, Prager BC, Flavahan WA, Liu X, Singer M, Hubert CG, Miller TE, Zhou W, Huang Z, Fang X, Regev A, Suvà ML, Hwang TH, Locasale JW, Bao S, Rich JN. Purine synthesis promotes maintenance of brain tumor initiating cells in glioma. Nature neuroscience. 2017 May;20(5):661–673.

Published In

Nature neuroscience

DOI

EISSN

1546-1726

ISSN

1097-6256

Publication Date

May 2017

Volume

20

Issue

5

Start / End Page

661 / 673

Related Subject Headings

  • Up-Regulation
  • Ribose-Phosphate Pyrophosphokinase
  • Purines
  • Proto-Oncogene Proteins c-myc
  • Neurology & Neurosurgery
  • Neoplastic Stem Cells
  • Metabolomics
  • Humans
  • Guanosine Monophosphate
  • Glycolysis