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PMID: 20570523 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

Glutamine addiction: a new therapeutic target in cancer.

Trends in biochemical sciences ·Vol. 35 ·No. 8 ·2010-08-00 ·Pages 427-33

Wise DR, Thompson CB

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.

MeSH Terms
Animals Glutamine/antagonists & inhibitors,blood,metabolism Humans Mitochondria/metabolism Molecular Targeted Therapy NADP/metabolism Neoplasms/drug therapy,metabolism,pathology Nucleotides/metabolism Protein Biosynthesis TOR Serine-Threonine Kinases/metabolism
Chemicals
Nucleotides Glutamine NADP TOR Serine-Threonine Kinases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Wise David R
Department of Cancer Biology, Abramson Cancer Center, University of Pennsylvania, Room 450, BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104-6160, USA.
Thompson Craig B
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Article Info
Journal
Trends in biochemical sciences
Abbr.
Trends Biochem Sci
ISSN
0968-0004
DOI
10.1016/j.tibs.2010.05.003
Published
2010-08-00
Pages
427-33
Language
English
Region
England
NLM ID
7610674
PMCID
PMC2917518
Subset
IM
Grants
NCI NIH HHS · R01 CA105463 · United States
NCI NIH HHS · R01 CA105463-08 · United States
External Links
PubMed source DOI: 10.1016/j.tibs.2010.05.003 PMC Full Text View journal details
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