Is Cancer a Metabolic Disease?

被引:179
作者
Coller, Hilary A. [1 ]
机构
[1] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA
关键词
PYRUVATE-DEHYDROGENASE KINASE; POSITRON-EMISSION-TOMOGRAPHY; SMALL-MOLECULE INHIBITION; ENDOTHELIAL GROWTH-FACTOR; HIGH LACTATE LEVELS; INDUCIBLE FACTOR-I; GLUCOSE-METABOLISM; AEROBIC GLYCOLYSIS; CELL-GROWTH; C-MYC;
D O I
10.1016/j.ajpath.2013.07.035
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Although cancer has historically been viewed as a disorder of proliferation, recent evidence has suggested that it should also be considered a metabolic disease. Growing tumors rewire their metabolic programs to meet and even exceed the bioenergetic and biosynthetic demands of continuous cell growth. The metabolic profile observed in cancer cells often includes increased consumption of glucose and glutamine, increased glycolysis, changes in the use of metabolic enzyme isoforms, and increased secretion of lactate. Oncogenes and tumor suppressors have been discovered to have roles in cancer-associated changes in metabolism as well. The metabolic profile of tumor cells has been suggested to reflect the rapid proliferative rate. Cancer-associated metabolic changes may also reveal the importance of protection against reactive oxygen species or a role for secreted lactate in the tumor microenvironment. This article reviews recent research in the field of cancer metabolism, raising the following questions: Why do cancer cells shift their metabolism in this way? Are the changes in metabolism in cancer cells a consequence of the changes in proliferation or a driver of cancer progression? Can cancer metabolism be targeted to benefit patients?
引用
收藏
页码:4 / 17
页数:14
相关论文
共 132 条
  • [21] p53 Negatively Regulates Transcription of the Pyruvate Dehydrogenase Kinase Pdk2
    Contractor, Tanupriya
    Harris, Chris R.
    [J]. CANCER RESEARCH, 2012, 72 (02) : 560 - 567
  • [22] Positron emission tomography scanning: Current and future applications
    Czernin, J
    Phelps, ME
    [J]. ANNUAL REVIEW OF MEDICINE, 2002, 53 : 89 - 112
  • [23] Beyond aerobic glycolysis: Transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis
    DeBerardinis, Ralph J.
    Mancuso, Anthony
    Daikhin, Evgueni
    Nissim, Ilana
    Yudkoff, Marc
    Wehrli, Suzanne
    Thompson, Craig B.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (49) : 19345 - 19350
  • [24] Phosphatidylinositol 3-kinase-dependent modulation of carnitine palmitoyltransferase 1A expression regulates lipid metabolism during hematopoietic cell growth
    DeBerardinis, Ralph J.
    Lum, Julian J.
    Thompson, Craig B.
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (49) : 37372 - 37380
  • [25] Phosphorylation and activation of heart 6-phosphofructo-2-kinase by protein kinase B and other protein kinases of the insulin signaling cascades
    Deprez, J
    Vertommen, D
    Alessi, DR
    Hue, L
    Rider, MH
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (28) : 17269 - 17275
  • [26] Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance
    Fantin, Valeria R.
    St-Pierre, Julie
    Leder, Philip
    [J]. CANCER CELL, 2006, 9 (06) : 425 - 434
  • [27] TEMPORARY REMISSIONS IN ACUTE LEUKEMIA IN CHILDREN PRODUCED BY FOLIC ACID ANTAGONIST, 4-AMINOPTEROYL-GLUTAMIC ACID (AMINOPTERIN)
    FARBER, S
    DIAMOND, LK
    MERCER, RD
    SYLVESTER, RF
    WOLFF, JA
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1948, 238 (23) : 787 - 793
  • [28] Targeting insulin inhibition as a metabolic therapy in advanced cancer: A pilot safety and feasibility dietary trial in 10 patients
    Fine, Eugene J.
    Segal-Isaacson, C. J.
    Feinman, Richard D.
    Herszkopf, Silvia
    Romano, Maria C.
    Tomuta, Norica
    Bontempo, Amanda F.
    Negassa, Abdissa
    Sparano, Joseph A.
    [J]. NUTRITION, 2012, 28 (10) : 1028 - 1035
  • [29] Inhibitory effect of tumor cell-derived lactic acid on human T cells
    Fischer, Karin
    Hoffmann, Petra
    Voelkl, Simon
    Meidenbauer, Norbert
    Ammer, Julia
    Edinger, Matthias
    Gottfried, Eva
    Schwarz, Sabine
    Rothe, Gregor
    Hoves, Sabine
    Renner, Kathrin
    Timischl, Birgit
    Mackensen, Andreas
    Kunz-Schughart, Leoni
    Andreesen, Reinhard
    Krause, Stefan W.
    Kreutz, Marina
    [J]. BLOOD, 2007, 109 (09) : 3812 - 3819
  • [30] Mitochondrial p32 Protein Is a Critical Regulator of Tumor Metabolism via Maintenance of Oxidative Phosphorylation
    Fogal, Valentina
    Richardson, Adam D.
    Karmali, Priya P.
    Scheffler, Immo E.
    Smith, Jeffrey W.
    Ruoslahti, Erkki
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2010, 30 (06) : 1303 - 1318