Glucose-independent glutamine-driven TCA cycle in cancer cells

Brad Poore, Nicholas Siegel, Joshua K. Park, Benjamin Jung Hwang, Iman Afif, Anne Le

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Although genetic alterations are ultimately believed to cause cancer, they can also lead to dysregulation of genes encoding metabolic enzymes that enables cancer cells to proliferate and metastasize. Even though the tricarboxylic acid (TCA) cycle is considered an oxidation pathway for glucose metabolism, Le et al. have demonstrated otherwise. Using stable isotope-resolved metabolomics to resolve 13C and 15N from labeled glucose or glutamine, they found that B-cell cancers maintain their TCA cycle solely relying on glutamine when glucose is withdrawn. This glucose-independent TCA cycle allows cancer cells to maintain its bioenergetics, catabolic, and anabolic needs under glucose limited conditions. The effect is so profound that certain cancer cells become addicted and cannot proliferate without glutamine, even in the presence of glucose. Due to glutamine’s emerging role in cancer, targeting the glutaminolysis pathway is a promising new approach to cancer therapy. Moreover, the results of their research demonstrated that inhibition of glutaminase, an enzyme that converts glutamine to glutamate, slows B-cell cancer growth. The ability of B-cell cancer cells to reprogram their metabolism by using glutamine instead of glucose to adapt to the nutrient availability in the tumor microenvironment confers a selective advantage for cancer cell survival and proliferation. This knowledge gives researchers a critical means by which to exploit the metabolic adaptations of these cancer cells and develop new cancer therapies.

Original languageEnglish (US)
Title of host publicationGlutamine in Clinical Nutrition
PublisherSpringer New York
Pages77-85
Number of pages9
ISBN (Electronic)9781493919321
ISBN (Print)9781493919314
DOIs
StatePublished - Jan 1 2015

Keywords

  • Glucose-deficient microenvironment
  • Glucose-independent glutamine-driven TCA cycle
  • Glutaminolysis
  • TCA cycle
  • Targeting glutamine metabolism

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Engineering(all)
  • Agricultural and Biological Sciences(all)

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  • Cite this

    Poore, B., Siegel, N., Park, J. K., Hwang, B. J., Afif, I., & Le, A. (2015). Glucose-independent glutamine-driven TCA cycle in cancer cells. In Glutamine in Clinical Nutrition (pp. 77-85). Springer New York. https://doi.org/10.1007/978-1-4939-1932-1_6