title: Glutaminolysis: A Hallmark of Cancer Metabolism.
abstract: Glutamine is the most abundant circulating amino acid in blood and muscle and is critical for many fundamental cell functions in cancer cells, including synthesis of metabolites that maintain mitochondrial metabolism; generation of antioxidants to remove reactive oxygen species; synthesis of nonessential amino acids (NEAAs), purines, pyrimidines, and fatty acids for cellular replication; and activation of cell signaling. In light of the pleiotropic role of glutamine in cancer cells, a comprehensive understanding of glutamine metabolism is essential for the development of metabolic therapeutic strategies for targeting cancer cells. In this article, we review oncogene-, tumor suppressor-, and tumor microenvironment-mediated regulation of glutamine metabolism in cancer cells. We describe the mechanism of glutamine's regulation of tumor proliferation, metastasis, and global methylation. Furthermore, we highlight the therapeutic potential of glutamine metabolism and emphasize that clinical application of in vivo assessment of glutamine metabolism is critical for identifying new ways to treat patients through glutamine-based metabolic therapy.
authors.affiliation: Laboratory for Systems Biology of Human Diseases, Rice University, Houston, Texas 77005.|Department of Chemical and Biomolecular Engineering, Rice University, Houston, Texas 77005.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109; email: svenneti@med.umich.edu.
authors.forename: Sriram
authors.initials: S
authors.lastname: Venneti
authors.affiliation: Laboratory for Systems Biology of Human Diseases, Rice University, Houston, Texas 77005.|Department of Chemical and Biomolecular Engineering, Rice University, Houston, Texas 77005.|Department of Bioengineering, Rice University, Houston, Texas 77005.|Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109; email: dnagrath@umich.edu.|Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan 48109.|Comprehensive Cancer Center, University of Michigan Health Systems, Ann Arbor, Michigan 48109.
authors.forename: Deepak
authors.initials: D
authors.lastname: Nagrath
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D014408:Biomarkers, Tumor; D005973:Glutamine
keywords: PET imaging; biosynthesis; cancer; global methylation; glutaminolysis; metabolic imaging; metastasis; proliferation; tumor microenvironment