Glutamine addiction: a new therapeutic target in cancer.
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.
Wise
David R
DR
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
CB
D000818:Animals; D005973:Glutamine / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009249:NADP / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D009711:Nucleotides / Q000378:metabolism; D014176:Protein Biosynthesis; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
D009711:Nucleotides; D005973:Glutamine; D009249:NADP; D058570:TOR Serine-Threonine Kinases