Glutamine and cancer: cell biology, physiology, and clinical opportunities

被引:995
作者
Hensley, Christopher T. [1 ]
Wasti, Ajla T. [1 ,2 ]
DeBerardinis, Ralph J. [1 ,2 ]
机构
[1] Univ Texas SW Med Ctr Dallas, Childrens Med Ctr Res Inst, Dallas, TX 75390 USA
[2] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA
关键词
X(C)(-) TRANSPORTER ACTIVITY; AMINO-ACIDS; METABOLISM; GLUCOSE; GROWTH; LUNG; MUSCLE; INHIBITION; EXPRESSION; TUMORS;
D O I
10.1172/JCI69600
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Glutamine is an abundant and versatile nutrient that participates in energy formation, redox homeostasis, macromolecular synthesis, and signaling in cancer cells. These characteristics make glutamine metabolism an appealing target for new clinical strategies to detect, monitor, and treat cancer. Here we review the metabolic functions of glutamine as a super nutrient and the surprising roles of glutamine in supporting the biological hallmarks of malignancy. We also review recent efforts in imaging and therapeutics to exploit tumor cell glutamine dependence, discuss some of the challenges in this arena, and suggest a disease-focused paradigm to deploy these emerging approaches.
引用
收藏
页码:3678 / 3684
页数:7
相关论文
共 81 条
[1]   METABOLISM AND ACTION OF AMINO-ACID ANALOG ANTICANCER AGENTS [J].
AHLUWALIA, GS ;
GREM, JL ;
HAO, Z ;
COONEY, DA .
PHARMACOLOGY & THERAPEUTICS, 1990, 46 (02) :243-271
[2]   GLUTAMINE-METABOLISM IN LYMPHOCYTES OF THE RAT [J].
ARDAWI, MSM ;
NEWSHOLME, EA .
BIOCHEMICAL JOURNAL, 1983, 212 (03) :835-842
[3]   GLUTAMINE AND GLUCOSE-METABOLISM IN HUMAN PERIPHERAL LYMPHOCYTES [J].
ARDAWI, MSM .
METABOLISM-CLINICAL AND EXPERIMENTAL, 1988, 37 (01) :99-103
[4]   (4S)-4-(3-18F-Fluoropropyl)-L-Glutamate for Imaging of xC- Transporter Activity in Hepatocellular Carcinoma Using PET: Preclinical and Exploratory Clinical Studies [J].
Baek, Sora ;
Mueller, Andre ;
Lim, Young-Suk ;
Lee, Han Chu ;
Lee, Young-Joo ;
Gong, Gyungyub ;
Kim, Jae Seung ;
Ryu, Jin-Sook ;
Oh, Seung Jun ;
Lee, Seung Jin ;
Bacher-Stier, Claudia ;
Fels, Lueder ;
Koglin, Norman ;
Schatz, Christoph A. ;
Dinkelborg, Ludger M. ;
Moon, Dae Hyuk .
JOURNAL OF NUCLEAR MEDICINE, 2013, 54 (01) :117-123
[5]   Exploratory Clinical Trial of (4S)-4-(3-[18F]fluoropropyl)-L-glutamate for Imaging xC Transporter Using Positron Emission Tomography in Patients with Non-Small Cell Lung or Breast Cancer [J].
Baek, Sora ;
Choi, Chang-Min ;
Ahn, Sei Hyun ;
Lee, Jong Won ;
Gong, Gyungyub ;
Ryu, Jin-Sook ;
Oh, Seung Jun ;
Bacher-Stier, Claudia ;
Fels, Lueder ;
Koglin, Norman ;
Hultsch, Christina ;
Schatz, Christoph A. ;
Dinkelborg, Ludger M. ;
Mittra, Erik S. ;
Gambhir, Sanjiv S. ;
Moon, Dae Hyuk .
CLINICAL CANCER RESEARCH, 2012, 18 (19) :5427-5437
[6]   Exchange facilitated indirect detection of hyperpolarized 15ND2-amido-glutamine [J].
Barb, A. W. ;
Hekmatyar, S. K. ;
Glushka, J. N. ;
Prestegard, J. H. .
JOURNAL OF MAGNETIC RESONANCE, 2011, 212 (02) :304-310
[7]   INTRACELLULAR FREE AMINO-ACID CONCENTRATION IN HUMAN MUSCLE-TISSUE [J].
BERGSTROM, J ;
FURST, P ;
NOREE, LO ;
VINNARS, E .
JOURNAL OF APPLIED PHYSIOLOGY, 1974, 36 (06) :693-697
[8]   MCT1-mediated transport of a toxic molecule is an effective strategy for targeting glycolytic tumors [J].
Birsoy, Kivanc ;
Wang, Tim ;
Possemato, Richard ;
Yilmaz, Omer H. ;
Koch, Catherine E. ;
Chen, Walter W. ;
Hutchins, Amanda W. ;
Gultekin, Yetis ;
Peterson, Tim R. ;
Carette, Jan E. ;
Brummelkamp, Thijn R. ;
Clish, Clary B. ;
Sabatini, David M. .
NATURE GENETICS, 2013, 45 (01) :104-U149
[9]   RENAL OXYGEN-CONSUMPTION, THERMOGENESIS, AND AMINO-ACID UTILIZATION DURING IV INFUSION OF AMINO-ACIDS IN MAN [J].
BRUNDIN, T ;
WAHREN, J .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 1994, 267 (05) :E648-E655
[10]   Deprive to kill Glutamine closes the gate to anticancer monocarboxylic drugs [J].
Cardaci, Simone ;
Ciriolo, Maria Rosa .
AUTOPHAGY, 2012, 8 (12) :1830-1832