Cited by 1,770Cancer, Hypoxia, and MetabolismAmino Acid Enzymes and MetabolismCancer, Lipids, and Metabolism

Glutamine addiction: a new therapeutic target in cancer

Open access
Wise, David R., Thompson, Craig B.·2010·Trends in Biochemical Sciences

Abstract

Most cancers depend on a high rate of aerobic glycolysis for their continued growth and survival. Paradoxically, some cancer cell lines also display addiction to glutamine despite the fact that glutamine is a nonessential amino acid that can be synthesized from glucose. The high rate of glutamine uptake exhibited by glutamine-dependent cells does not appear to result solely from its role as a nitrogen donor in nucleotide and amino acid biosynthesis. Instead, glutamine plays a required role in the uptake of essential amino acids and in maintaining activation of TOR (target of rapamycin) kinase. Moreover, in many cancer cells, glutamine is the primary mitochondrial substrate and is required for maintenance of mitochondrial membrane potential and integrity and for support of the NADPH production needed for redox control and macromolecular synthesis.

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Crossref · 10.1016/j.tibs.2010.05.003

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  1. [48]Yuneva M 2007 Deficiency in glutamine but not glucose induces MYC-dependent apoptosis in human cells J Cell Biol 178 93 105 17606868 PMC2064426

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Authors
Wise, D. R., & Thompson, C. B.
Affiliations
Abramson Cancer Center (US)
Corresponding author
Thompson, Craig B.
Venue
Trends in Biochemical Sciences
Publisher
Elsevier BV
Published
2010-08
Volume
35
Issue
8
Pages
427-433
ISSN
0968-0004 (ISSN-L)
OpenAlex
W2090406819
Cited by
1,770
References
71
Citations by year
2026: 67 · 2025: 113 · 2024: 122 · 2023: 115 · 2022: 144 · 2021: 154 · 2020: 140 · 2019: 159 · 2018: 138 · 2017: 139 · 2016: 133 · 2015: 108 · 2014: 93 · 2013: 64 · 2012: 54
FWCI
3.80
Type
journal article
Language
en
Open access
Locations
  • Trends in Biochemical Sciences (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Cancer Institute (R01CA105463)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords
glutamine addiction, cancer metabolism, glutamine uptake, aerobic glycolysis, TOR kinase, mitochondrial metabolism, mitochondrial membrane potential, NADPH production, redox regulation, therapeutic target
MeSH terms
Animals, Glutamine, Humans, Mitochondria, NADP, Neoplasms, Nucleotides, Protein Biosynthesis, TOR Serine-Threonine Kinases, Molecular Targeted Therapy

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