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

被引：1002
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
来源：
JOURNAL OF CLINICAL INVESTIGATION | 2013年 / 123卷 / 09期
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
[21]   13C MR spectroscopy measurements of glutaminase activity in human hepatocellular carcinoma cells using hyperpolarized 13C-labeled glutamine [J].
Gallagher, Ferdia A. ;
Kettunen, Mikko I. ;
Day, Sam E. ;
Lerche, Mathilde ;
Brindle, Kevin M. .
MAGNETIC RESONANCE IN MEDICINE, 2008, 60 (02) :253-257
[22]   c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism [J].
Gao, Ping ;
Tchernyshyov, Irina ;
Chang, Tsung-Cheng ;
Lee, Yun-Sil ;
Kita, Kayoko ;
Ochi, Takafumi ;
Zeller, Karen I. ;
De Marzo, Angelo M. ;
Van Eyk, Jennifer E. ;
Mendell, Joshua T. ;
Dang, Chi V. .
NATURE, 2009, 458 (7239) :762-U100
[23]   Hallmarks of Cancer: The Next Generation [J].
Hanahan, Douglas ;
Weinberg, Robert A. .
CELL, 2011, 144 (05) :646-674
[24]   SLC1A5 Mediates Glutamine Transport Required for Lung Cancer Cell Growth and Survival [J].
Hassanein, Mohamed ;
Hoeksema, Megan D. ;
Shiota, Masakazu ;
Qian, Jun ;
Harris, Bradford K. ;
Chen, Heidi ;
Clark, Jonathan E. ;
Alborn, William E. ;
Eisenberg, Rosana ;
Massion, Pierre P. .
CLINICAL CANCER RESEARCH, 2013, 19 (03) :560-570
[25]   Pulmonary glutamine production:: effects of sepsis and pulmonary infiltrates [J].
Hulsewé, KWE ;
van der Hulst, RRWJ ;
Ramsay, G ;
van Berlo, CLH ;
Deutz, NEP ;
Soeters, PB .
INTENSIVE CARE MEDICINE, 2003, 29 (10) :1833-1836
[26]   Reciprocal regulation of p53 and malic enzymes modulates metabolism and senescence [J].
Jiang, Peng ;
Du, Wenjing ;
Mancuso, Anthony ;
Wellen, Kathryn E. ;
Yang, Xiaolu .
NATURE, 2013, 493 (7434) :689-+
[27]   Glutamine-dependent anapleurosis dictates glucose uptake and cell growth by regulating MondoA transcriptional activity [J].
Kaadige, Mohan R. ;
Looper, Ryan E. ;
Kamalanaadhan, Sadhaasivam ;
Ayer, Donald E. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (35) :14878-14883
[28]   Specific PET Imaging of xC- Transporter Activity Using a 18F-Labeled Glutamate Derivative Reveals a Dominant Pathway in Tumor Metabolism [J].
Koglin, Norman ;
Mueller, Andre ;
Berndt, Mathias ;
Schmitt-Willich, Heribert ;
Toschi, Luisella ;
Stephens, Andrew W. ;
Gekeler, Volker ;
Friebe, Matthias ;
Dinkelborg, Ludger M. .
CLINICAL CANCER RESEARCH, 2011, 17 (18) :6000-6011
[29]   Glutamine Synthetase Is a Genetic Determinant of Cell Type-Specific Glutamine Independence in Breast Epithelia [J].
Kung, Hsiu-Ni ;
Marks, Jeffrey R. ;
Chi, Jen-Tsan .
PLOS GENETICS, 2011, 7 (08)
[30]   Analysis of Cancer Metabolism by Imaging Hyperpolarized Nuclei: Prospects for Translation to Clinical Research [J].
Kurhanewicz, John ;
Vigneron, Daniel B. ;
Brindle, Kevin ;
Chekmenev, Eduard Y. ;
Comment, Arnaud ;
Cunningham, Charles H. ;
DeBerardinis, Ralph J. ;
Green, Gary G. ;
Leach, Martin O. ;
Rajan, Sunder S. ;
Rizi, Rahim R. ;
Ross, Brian D. ;
Warren, Warren S. ;
Malloy, Craig R. .
NEOPLASIA, 2011, 13 (02) :81-97
123456789