Links between metabolism and cancer

被引:802
|
作者
Dang, Chi V. [1 ]
机构
[1] Univ Penn, Perelman Sch Med, Abramson Family Canc Res Inst, Abramson Canc Ctr,Div Hematol Oncol,Dept Med, Philadelphia, PA 19104 USA
关键词
caloric restriction; cancer; glycolysis; metabolism; obesity; oncogenes; tumor suppressors; MAMMALIAN-CELL GROWTH; C-MYC; GLUTAMINE-METABOLISM; TUMOR-CELLS; ONCOMETABOLITE; 2-HYDROXYGLUTARATE; TRANSCRIPTIONAL ACTIVITY; P53-INDUCIBLE REGULATOR; RIBOSOMAL BIOGENESIS; ALPHA-KETOGLUTARATE; GLUCOSE-METABOLISM;
D O I
10.1101/gad.189365.112
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Metabolism generates oxygen radicals, which contribute to oncogenic mutations. Activated oncogenes and loss of tumor suppressors in turn alter metabolism and induce aerobic glycolysis. Aerobic glycolysis or the Warburg effect links the high rate of glucose fermentation to cancer. Together with glutamine, glucose via glycolysis provides the carbon skeletons, NADPH, and ATP to build new cancer cells, which persist in hypoxia that in turn rewires metabolic pathways for cell growth and survival. Excessive caloric intake is associated with an increased risk for cancers, while caloric restriction is protective, perhaps through clearance of mitochondria or mitophagy, thereby reducing oxidative stress. Hence, the links between metabolism and cancer are multifaceted, spanning from the low incidence of cancer in large mammals with low specific metabolic rates to altered cancer cell metabolism resulting from mutated enzymes or cancer genes.
引用
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页码:877 / 890
页数:14
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