Crucial role of the pentose phosphate pathway in malignant tumors

Abstract

Interest in cancer metabolism has increased in recent years. The pentose phosphate pathway (PPP) is a major glucose catabolism pathway that directs glucose flux to its oxidative branch and leads to the production of a reduced form of nicotinamide adenine dinucleotide phosphate and nucleic acid. The PPP serves a vital role in regulating cancer cell growth and involves many enzymes. The aim of the present review was to describe the recent discoveries associated with the deregulatory mechanisms of the PPP and glycolysis in malignant tumors, particularly in hepatocellular carcinoma, breast and lung cancer.

Keywords: breast cancer; glycolysis; hepatocellular carcinoma; pentose phosphate pathway.

Figure 1.

PPP. G6PD converts glucose-6-phosphate into 6-phosphogluconolactone. 6-Phosphogluconolactone then converted to Ru5P by 6PGD. Ru5P undergoes isomerization by RPI or RPE to generate ribose-5-phosphate or xylulose-5-phosphate, respectively. In the non-oxidative reactions of PPP, TKT and TALDO are responsible for relatively complex interconversion reactions. Curved arrows indicate that G6PD, 6PGD, RPI, TKT and TALDO are overexpressed in cancer cells. 6PGD, 6-phosphogluconate dehydrogenase; G6PD, glucose 6-phosphate dehydrogenase; PPP, pentose phosphate pathway; RPE, ribulose-5-phosphate epimerase; RPI, ribose 5-phosphate isomerase; Ru5P, ribulose-5-phosphate; TALDO, transaldolase; TKT, transketolase.

Figure 2.

Glycolysis. Glycolysis consists of two stages, the first stage consuming ATP and the second stage generating ATP. There are three crucial reactions in tumor cells. First, HK catalyzes the conversion of glucose to glucose-6-phosphate. Second, fructose-6-phosphate is converted into fructose 1,6-bisphosphate by PFK1, and fructose 1,6-bisphosphate is converted into fructose 2,6-bisphosphate by PFK2. Third, phosphoenolpyruvate is converted into pyruvate by PK. Curved arrows indicate that HK, PFK1 and PK are overexpressed in cancer cells. HK, hexokinase; PK, pyruvate kinase; PFK, phosphofructokinase.