Skip to main content

Activation of the NRF2 antioxidant program generates an imbalance in central carbon metabolism in cancer.

Publication ,  Journal Article
Sayin, VI; LeBoeuf, SE; Singh, SX; Davidson, SM; Biancur, D; Guzelhan, BS; Alvarez, SW; Wu, WL; Karakousi, TR; Zavitsanou, AM; Ubriaco, J ...
Published in: Elife
October 2, 2017

During tumorigenesis, the high metabolic demand of cancer cells results in increased production of reactive oxygen species. To maintain oxidative homeostasis, tumor cells increase their antioxidant production through hyperactivation of the NRF2 pathway, which promotes tumor cell growth. Despite the extensive characterization of NRF2-driven metabolic rewiring, little is known about the metabolic liabilities generated by this reprogramming. Here, we show that activation of NRF2, in either mouse or human cancer cells, leads to increased dependency on exogenous glutamine through increased consumption of glutamate for glutathione synthesis and glutamate secretion by xc- antiporter system. Together, this limits glutamate availability for the tricarboxylic acid cycle and other biosynthetic reactions creating a metabolic bottleneck. Cancers with genetic or pharmacological activation of the NRF2 antioxidant pathway have a metabolic imbalance between supporting increased antioxidant capacity over central carbon metabolism, which can be therapeutically exploited.

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Elife

DOI

EISSN

2050-084X

Publication Date

October 2, 2017

Volume

6

Location

England

Related Subject Headings

  • Neoplasms
  • NF-E2-Related Factor 2
  • Mice
  • Humans
  • Homeostasis
  • Glutathione
  • Glutamic Acid
  • Cell Survival
  • Cell Proliferation
  • Cell Line, Tumor
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Sayin, V. I., LeBoeuf, S. E., Singh, S. X., Davidson, S. M., Biancur, D., Guzelhan, B. S., … Papagiannakopoulos, T. (2017). Activation of the NRF2 antioxidant program generates an imbalance in central carbon metabolism in cancer. Elife, 6. https://doi.org/10.7554/eLife.28083
Sayin, Volkan I., Sarah E. LeBoeuf, Simranjit X. Singh, Shawn M. Davidson, Douglas Biancur, Betul S. Guzelhan, Samantha W. Alvarez, et al. “Activation of the NRF2 antioxidant program generates an imbalance in central carbon metabolism in cancer.Elife 6 (October 2, 2017). https://doi.org/10.7554/eLife.28083.
Sayin VI, LeBoeuf SE, Singh SX, Davidson SM, Biancur D, Guzelhan BS, et al. Activation of the NRF2 antioxidant program generates an imbalance in central carbon metabolism in cancer. Elife. 2017 Oct 2;6.
Sayin, Volkan I., et al. “Activation of the NRF2 antioxidant program generates an imbalance in central carbon metabolism in cancer.Elife, vol. 6, Oct. 2017. Pubmed, doi:10.7554/eLife.28083.
Sayin VI, LeBoeuf SE, Singh SX, Davidson SM, Biancur D, Guzelhan BS, Alvarez SW, Wu WL, Karakousi TR, Zavitsanou AM, Ubriaco J, Muir A, Karagiannis D, Morris PJ, Thomas CJ, Possemato R, Vander Heiden MG, Papagiannakopoulos T. Activation of the NRF2 antioxidant program generates an imbalance in central carbon metabolism in cancer. Elife. 2017 Oct 2;6.

Published In

Elife

DOI

EISSN

2050-084X

Publication Date

October 2, 2017

Volume

6

Location

England

Related Subject Headings

  • Neoplasms
  • NF-E2-Related Factor 2
  • Mice
  • Humans
  • Homeostasis
  • Glutathione
  • Glutamic Acid
  • Cell Survival
  • Cell Proliferation
  • Cell Line, Tumor