Abstract
Energy metabolism is significantly reprogrammed in many human cancers, and these alterations confer many advantages to cancer cells, including the promotion of biosynthesis, ATP generation, detoxification and support of rapid proliferation. The pentose phosphate pathway (PPP) is a major pathway for glucose catabolism. The PPP directs glucose flux to its oxidative branch and produces a reduced form of nicotinamide adenine dinucleotide phosphate (NADPH), an essential reductant in anabolic processes. It has become clear that the PPP plays a critical role in regulating cancer cell growth by supplying cells with not only ribose-5-phosphate but also NADPH for detoxification of intracellular reactive oxygen species, reductive biosynthesis and ribose biogenesis. Thus, alteration of the PPP contributes directly to cell proliferation, survival and senescence. Furthermore, recent studies have shown that the PPP is regulated oncogenically and/or metabolically by numerous factors, including tumor suppressors, oncoproteins and intracellular metabolites. Dysregulation of PPP flux dramatically impacts cancer growth and survival. Therefore, a better understanding of how the PPP is reprogrammed and the mechanism underlying the balance between glycolysis and PPP flux in cancer will be valuable in developing therapeutic strategies targeting this pathway.
Highlights
Tumor cells have long been known to reprogram their energy metabolism to meet high biogenetic demands in support of rapid and uncontrolled growth
A better understanding of how the phosphate pathway (PPP) is reprogrammed and the mechanism underlying the balance between glycolysis and PPP flux in cancer will be valuable in developing therapeutic strategies targeting this pathway
glucose-6-phosphate dehydrogenase (G6PD) directly controls the PPP flux, which generates R5P for the biosynthesis of nucleotides and nicotinamide adenine dinucleotide phosphate (NADPH) for reductive biosynthesis and ROS scavenging, and high G6PD activity is expected to result in an increase in the biosynthesis of lipids and DNA, which are both needed for cell division and proliferation
Summary
Tumor cells have long been known to reprogram their energy metabolism to meet high biogenetic demands in support of rapid and uncontrolled growth. KEYWORDS pentose phosphate pathway (PPP), G6PD, NADPH, glucose metabolism, cancer, cell proliferation
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