Cancer Metabolism: Fueling More than Just Growth

被引:74
作者
Lee, Namgyu [1 ]
Kim, Dohoon [1 ]
机构
[1] Univ Massachusetts, Sch Med, Dept Mol Cell & Canc Biol, Worcester, MA 01655 USA
关键词
cancer; immune evasion; metabolism; metabolites; tumor microenvironment; PYRUVATE-KINASE M2; LACTIC-ACID; STEM-CELLS; ONCOMETABOLITE; 2-HYDROXYGLUTARATE; ADENOSINE RECEPTORS; ALTERED METABOLISM; IMMUNE CELLS; TUMOR; HYPOXIA; MACROPHAGES;
D O I
10.14348/molcells.2016.0310
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The early landmark discoveries in cancer metabolism research have uncovered metabolic processes that support rapid proliferation, such as aerobic glycolysis (Warburg effect), glutaminolysis, and increased nucleotide biosynthesis. However, there are limitations to the effectiveness of specifically targeting the metabolic processes which support rapid proliferation. First, as other normal proliferative tissues also share similar metabolic features, they may also be affected by such treatments. Secondly, targeting proliferative metabolism may only target the highly proliferating "bulk tumor" cells and not the slower-growing, clinically relevant cancer stem cell subpopulations which may be required for an effective cure. An emerging body of research indicates that altered metabolism plays key roles in supporting proliferation-independent functions of cancer such as cell survival within the ischemic and acidic tumor microenvironment, immune system evasion, and maintenance of the cancer stem cell state. As these aspects of cancer cell metabolism are critical for tumor maintenance yet are less likely to be relevant in normal cells, they represent attractive targets for cancer therapy.
引用
收藏
页码:847 / 854
页数:8
相关论文
共 87 条
[51]   Pyruvate Kinase M2 Is a PHD3-Stimulated Coactivator for Hypoxia-Inducible Factor 1 [J].
Luo, Weibo ;
Hu, Hongxia ;
Chang, Ryan ;
Zhong, Jun ;
Knabel, Matthew ;
O'Meally, Robert ;
Cole, Robert N. ;
Pandey, Akhilesh ;
Semenza, Gregg L. .
CELL, 2011, 145 (05) :732-744
[52]   Anticancer antifolates: Current status and future directions. [J].
McGuire, JJ .
CURRENT PHARMACEUTICAL DESIGN, 2003, 9 (31) :2593-2613
[53]   Hypoxia-inducing factors as master regulators of stemness properties and altered metabolism of cancer- and metastasis-initiating cells [J].
Mimeault, Murielle ;
Batra, Surinder K. .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2013, 17 (01) :30-54
[54]   Quiescent, Slow-Cycling StemCell Populations in Cancer: A Review of the Evidence and Discussion of Significance [J].
Moore, Nathan ;
Lyle, Stephen .
JOURNAL OF ONCOLOGY, 2011, 2011
[55]   Indoleamine 2,3-dioxygenase and tumor-induced tolerance [J].
Munn, David H. ;
Mellor, Andrew L. .
JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (05) :1147-1154
[56]  
Neumann HPH, 2004, JAMA-J AM MED ASSOC, V292, P943, DOI 10.1001/jama.292.8.943
[57]   HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption [J].
Papandreou, I ;
Cairns, RA ;
Fontana, L ;
Lim, AL ;
Denko, NC .
CELL METABOLISM, 2006, 3 (03) :187-197
[58]   pH Control Mechanisms of Tumor Survival and Growth [J].
Parks, Scott K. ;
Chiche, Johanna ;
Pouyssegur, Jacques .
JOURNAL OF CELLULAR PHYSIOLOGY, 2011, 226 (02) :299-308
[59]   Metabolic Pathways in Immune Cell Activation and Quiescence [J].
Pearce, Erika L. ;
Pearce, Edward J. .
IMMUNITY, 2013, 38 (04) :633-643
[60]   Reversal of tumoral immune resistance by inhibition of tryptophan 2,3-dioxygenase [J].
Pilotte, Luc ;
Larrieu, Pierre ;
Stroobant, Vincent ;
Colau, Didier ;
Dolusic, Eduard ;
Frederick, Raphael ;
De Plaen, Etienne ;
Uyttenhove, Catherine ;
Wouters, Johan ;
Masereel, Bernard ;
Van den Eynde, Benoit J. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (07) :2497-2502