Glutaminolysis: A Hallmark of Cancer Metabolism.
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.
['Yang|Lifeng|L|', 'Venneti|Sriram|S|', 'Nagrath|Deepak|D|']
D000818:Animals D014408:Biomarkers, Tumor D049109:Cell Proliferation D002471:Cell Transformation, Neoplastic D005973:Glutamine D006801:Humans D008928:Mitochondria D008954:Models, Biological D009369:Neoplasms D015398:Signal Transduction
glutaminolysis cancer proliferation metastasis global methylation PET imaging biosynthesis metabolic imaging tumor microenvironment