The study found a new mechanism for reprogramming the metabolism of liver cancer.

Recently, the international academic journal Nature cancer published online the latest research results of Yin Huiyong, Shanghai Institute of nutrition and health, Chinese Academy of Sciences, which clarified the role, mechanism and clinical significance of fructose-1,6-diphosphate (FBP) aldolase B (aldob) in regulating metabolic reprogramming of liver cancer.metabolic abnormality is one of the important characteristics of tumor. Tumor cells will undergo a series of metabolic reprogramming to meet the needs of rapid proliferation.Warburg effect proposed in 1920sEven under aerobic conditions, tumor cells can produce energy and raw materials for cell proliferation by anaerobic glycolysis.therefore, the molecular mechanism and clinical significance of tumor cell metabolic reprogramming have been one of the important directions in the field of tumor research.recent studies have found that tumor cells can realize metabolic reprogramming by using gene mutation, epigenetic changes, protein-protein interaction and the interaction between metabolic enzymes and metabolites.aldolase catalyzes the cleavage of FBP to produce dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (GAP) in glycolysis, and the reverse reaction of DHAP and gap to produce FBP in gluconeogenesis.aldob was mainly expressed in liver, small intestine and kidney. The expression of aldob was down-regulated in HCC tissues. However, the molecular mechanism and clinical significance of aldob in the metabolic regulation of hepatocellular carcinoma (HCC) remain to be clarified.in this study, based on gene chip analysis of HCC patients' tissues, the researchers found that the expression of aldob was significantly down regulated in HCC patients' tumor tissues, and the expression of glucose-6-phosphate dehydrogenase (G6PD), the rate limiting enzyme of pentose phosphate pathway, was significantly up-regulated; patients with low expression of aldob and high expression of G6PD had a short survival period and poor prognosis, and aldob could be an independent risk factor for HCC.then, the researchers used aldob whole body or liver specific knockout mice, and found that the tumorigenesis of aldob knockout mice was significantly increased after N-nitrosodiethylamine (DEN) - induced HCC mice. Compared with para cancerous tissues, the activity of G6PD and PPP metabolic flow in tumor tissues were up-regulated; in liver specific knockout mice, the expression of aldob was significantly inhibited, and G6PD was chemically inhibited Both the enzyme activity and the down-regulation of G6PD expression at the gene level inhibited the tumorigenesis induced by aldob deletion.mechanism studies found that in normal hepatocytes, aldob and G6PD inhibit G6PD enzyme activity through direct protein interaction; at the same time, aldob can significantly enhance the inhibitory effect of tumor suppressor gene p53 on G6PD.in tumor cells, the down-regulation of aldob expression relieves the inhibition of G6PD, which leads to the enhancement of PPP metabolism and provides the synthetic raw materials and NADPH needed for the rapid growth of tumor cellsAnd glutathione.the results are supported by metabonomics and a variety of stable isotope metabolic flow data.in conclusion, this study elucidates a new molecular mechanism of cell metabolism regulation: the interaction between aldob and G6PD, two important metabolic enzymes in glycolysis and pentose phosphate pathway, regulates cell metabolism; the loss of aldob in tumor cells promotes its metabolic remodeling to promote tumor growth.this study found a new non enzyme function of aldob, and also suggested the value of the expression and interaction of aldob and G6PD in the clinical diagnosis and treatment of liver cancer.Yin Huiyong, researcher of Institute of nutrition and health, Tao Yongzhen, assistant researcher, and Cheng shuqun, director of the Third Affiliated Hospital of Naval Military Medical University, are corresponding authors of this paper. Li Min, he Xuxiao, doctoral students of Institute of nutrition and health, and Guo Weixing, doctor of the Third Affiliated Hospital of Naval Military Medical University, are co authors of the paper.the research was supported by the National Natural Science Foundation of China, the Ministry of science and technology and the Chinese Academy of Sciences.molecular mechanism of glycolytic enzyme aldob regulating metabolic remodeling of hepatocellular carcinoma source: Shanghai Institute of nutrition and health, Chinese Academy of Sciences