Research advances in abnormal gluconeogenesis in hepatocellular carcinoma / 临床肝胆病杂志

ABSTRACT

Tumors still perform glycolysis in the aerobic environment to accelerate the uptake of glucose and produce a large amount of lactic acid in tumor microenvironment, provide biomolecular precursors of nucleotides, lipids, and proteins for tumor cell proliferation, and inhibit the function of immune cells and promote the metastasis of tumor cells in acidic environment. Gluconeogenesis, as the reverse reaction of glycolysis, is inhibited in hepatocellular carcinoma, especially the downregulated expression of the four key rate-limiting enzymes pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1, 6-diphosphate 1, and glucose-6-phosphatase 4, which promotes the growth and proliferation of hepatocellular carcinoma by promoting aerobic glycolysis and its branched pathways, and meanwhile, it is also associated with the overall survival time and prognosis of patients with hepatocellular carcinoma and is considered an inhibitor for hepatocellular carcinoma. Therefore, this review summarizes the changes and mechanism of action of the key enzymes of gluconeogenesis in the development and progression of hepatocellular carcinoma and analyzes the shortcomings and future directions of related research in hepatocellular carcinoma, so as to provide new ideas for the treatment of hepatocellular carcinoma.