In collaboration with the Institute of Nutrition and Health, a new mechanism for reprogramming to regulate liver cancer metabolism has been discovered.

On July 6, 2020, 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, entitled "aldolase B suppresses endothelial carcinogenesis by inhibiting G6PD and pentose phosphate pathways", The role, mechanism and clinical significance of aldolase B (aldob) in the regulation of metabolic reprogramming in hepatocellular carcinoma.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.the Warburg effect proposed in the 1920s pointed out that even 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 in glycolysis to produce dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (GAP), and the reverse reaction of DHAP and gap to produce FBP in gluconeogenesis.aldob was mainly expressed in liver, small intestine and kidney.previous studies have found that the expression of aldob is down-regulated in hepatocellular carcinoma and its expression is associated with prognosis. However, the molecular mechanism and clinical significance of aldob in the metabolic regulation of hepatocellular carcinoma (HCC) remain to be clarified. The incidence rate ofis the sixth place in all cancers worldwide, and the mortality rate is fourth.China is a big country of liver cancer, and more than 55% of the new cases of liver cancer are in China every year.in this study, we found that the expression of aldob was significantly down-regulated in HCC patients' tumor tissues, and glucose-6-phosphate dehydrogenase (glucose-6-phosphate dehydrogenase), a rate limiting enzyme in the pentose phosphate pathway, was found in HCC patients, The patients with low expression of aldob and high expression of G6PD had short survival time and poor prognosis, and aldob could be an independent risk factor for HCC.next, the researchers used aldob whole body or liver specific knockout mice, and used N-nitrosodiethylamine, In the HCC mice model induced by den, the tumorigenesis was significantly aggravated after aldob knockout. Compared with the adjacent tissues, the activity of G6PD and PPP metabolic flow in tumor tissues were up-regulated; the tumor formation was significantly inhibited by the supplement of aldob expression in liver specific knockout mice; the tumor formation induced by aldob deletion was inhibited by chemical inhibition of G6PD enzyme activity or down-regulation of G6PD expression at gene level.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 materials needed for rapid growth of tumor cells, as well as NADPH and glutathione (as shown in the figure).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. Professor Yin Huiyong and assistant researcher Tao Yongzhen of Shanghai Institute of nutrition and health, Chinese Academy of Sciences, and Cheng shuqun, director of the Third Affiliated Hospital of Naval Military Medical University, are the corresponding authors of the paper. Li Min and he Xuxiao, doctoral students of Shanghai Institute of nutrition and health, Chinese Academy of Sciences, and Dr. Guo Weixing, the Third Affiliated Hospital of Naval Military Medical University, are the co authors of the paper. this work has been strongly supported by Li dangsheng and Ding Jianping, researcher Li Yu, Shanghai Institute of nutrition and health, Chinese Academy of Sciences, and Professor Lin Shengcai and Lin Shuhai of Xiamen University. this project is supported by the National Natural Science Foundation of China, the Ministry of science and technology and the Chinese Academy of Sciences. . 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