Cancer metabolism in gastrointestinal cancer

Abstract

Cancer cells exhibit altered glucose metabolism, mitochondrial dysfunction, anaerobic glycolysis, and upregulation of the pentose phosphate pathway (PPP). Recent genetic and metabolic analyses have provided insights into the molecular mechanisms of genes that are involved in alteration of cancer metabolism and tumorigenesis. Hypoxic induced factor 1 regulates the reciprocal relationship between glycolysis and oxidative phosphorylation, and p53 also modulates the balance between the glycolytic pathway and oxidative phosphorylation. Mitochondria function in cancer differs from that in normal cells owing to mutations of mitochondrial DNA and alterations of metabolism. Overexpression of transcription factors, metabolite transporters, and glycolytic enzymes is observed and associated with poor prognosis, and it may be associated with chemoradiotherapy resistance in multiple cancer cell types. The PPP plays a critical role in regulating cancer cell growth by supplying cells with ribose-5-phosphate and nicotinamide adenine dinucleotide phosphate for detoxification of intracellular reactive oxygen species (ROS), reductive biosynthesis, and ribose biogenesis. ROS levels increase during carcinogenesis owing to metabolic aberrations. This review discusses alterations of mitochondrial metabolism, anaerobic glycolysis, the PPP, and control of ROS levels by the endogenous antioxidant system in cancer, as well as the novel small molecules targeting these enzymes or transporters that exert antiproliferative effects.

Keywords

Anti-oxidants / cancer metabolism / mitochondria / pentose phosphate pathway / reactive oxygen species / Warburg effect

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