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Drivers of Glucose and Glutamine Metabolism Reprogramming in Tumor Cells and Their Potential as Target for Cancer

Abraham Nigussie Mekuria and Abraham Degaga Abdi

Malignant cells undergo a metabolic transformation to satisfy the demands of growth and proliferation. This metabolic reprogramming has been considered as an emerging hallmark of cancer. It is well established that most normal cells get energy first via glycolysis in the cytosol that is followed by mitochondrial oxidative phosphorylation (OXPHO) under aerobic conditions but when oxygen is scarce, glycolysis rather than OXPHO for energy supply. However, cancer cells prefer to perform glycolysis in the cytosol even in the presence of oxygen, a phenomenon first observed by Otto Warburg and now famously known as ‘’Warburg effect’’ or ‘’aerobic glycolysis’’. Such reprogramming of glucose metabolism has been validated within many tumors, and increased glycolysis facilitates biosynthesis of biomass (e.g., nucleotides, amino acids and lipids) by providing glycolytic intermediates as raw material. Besides the dysregulation of glucose metabolism, metabolic reprogramming in cancer cells has been characterized by aberrant lipid metabolism, amino acids metabolism, mitochondrial biogenesis, and other bioenergetics metabolic pathways. However, the two noticeable characteristics of tumor cell metabolism are the Warburg effect and glutaminolysis, which, respectively, demonstrate the dependence of tumor cells on glucose and glutamine. Investigation on these metabolic changes would uncover fundamental molecular events of malignancy and help to find better ways to diagnose and treat cancer. This review aimed at appraising recent findings related to the drivers of glucose and glutamine metabolism reprogramming, their crosstalk in cancer cells, and their potential in cancer therapy.