Role of glycolysis in breast cancer

Document Type : Original Article

Author

Faculty of pharmacy SCU

Abstract

Breast cancer is one of the most common cancer types in women with a high death rate worldwide.
Disturbance in glucose metabolism was proposed to be a pathogenetic mechanism of breast cancer. The Warburg’s effect in cancer is considered an important cell metabolic reprogramming process. Tumor causes an increase in aerobic glycolysis uncoupled with glucose oxidation leading to rise in glucose uptake, lactate production and reduction in oxidative phosphorylation. Therefore, this reprogramming increases the persistence of cancer cells with low adenosine triphosphate (ATP) yield and this is associated with mitochondrial respiration inhibition.
Consequently, this metabolic alteration provides cancer cell with a survival advantage because the high rate of aerobic glycolysis in cancer leads to increase of glycolytic branching pathways including PPP and SBP which supply cancer cell with NADPH, nucleotides and amino acids.
Furthermore, the inhibition of mitochondrial GO supplies cancer cell with apoptosis resistance. The enhancing of PDC and GO (PDK inhibition) in cancer cells leads to increase in the mitochondrial membrane potential, that furthermore increases the threshold of activation of the mitochondrial permeability transition pore and mitochondrial dependent apoptosis.

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