Mechanism Of Glycolysis And Fatty Acid β Oxidation Abnormal Activation Of Nasopharyngeal Carcinoma

The occurrence and development of tumor is a long-term and multi-step process with multi-factors involved in (physical factors, chemical factors and biological factors). More and more evidence suggests that the metabolism of cancer cells model has undergone significant changes, which involves glycolysis, citric acid cycle, oxidative phosphorylation, amino acid metabolism, fatty acid metabolism and nucleic acid metabolism, and many other aspects, the researchers defined this phenomenon as metabolic reprogramming of tumor cells.Metabolic reprogramming of tumor cells not only is the result of disorders in intracellular regulatory networks, but also is an important biochemical basis to maintain the malignant phenotype of tumor cells. A review article called "Hallmarks of Cancer:The Next Generation" published on "Cell" in2011writing by American Whitehead Institute Professor Robert A. Weinberg, pointing out that the metabolic reprogramming of tumor was the seventh major feature of the tumor, the others are self-activation of growth signal, insensitivity to the growth inhibition signal, escape from apoptosis, limitless replicative capacity sustained angiogenesis and tissue invasion. So metabolic disorders of cancer and its molecular basis are becoming an important cancer research direction.Our study focused on the metabolic reprogramming of nasopharyngeal carcinoma cells, we found the metabolic spectrum changes in nasopharyngeal carcinoma cells using high-throughput metabolomics analysis, glucose metabolism, Krebs cycle, multiple metabolic pathways of fat metabolism showed activation state. LMP1is a EB virus-encoded oncogene, regulates tumor cell proliferation differentiation, transformation and apoptosis through NF-kappaB, PI3-K/Akt, MAPK and Myc and many of the cancerous cells during the aberrant activation of signal transduction pathways. Studies have confirmed that PI3-K/Akt signal transduction pathway and Myc are tumor cell energy metabolism reprogramming process core molecules, In the first part of this topic, we clear the EB virus encoded latent membrane protein LMP1through PI3K/Akt signaling pathway for the regulation of sugar kinase HK2proves that LMP1by catalytic GSK3phosphorylation of serine nine beta, negative regulating GSK3beta activity, make the GSK3beta catalytic c-Myc threonine58ability is reduced, increase the c-Myc protein stability, so as to increase the expression of c-Myc, realize the regulation of HK2.This part of the study to establish a EBV-LMP1â†'PI3K/Aktâ†'GSK3β/FBW7â†'c-Mycâ†'HK2new signal transduction pathway, providing a new experimental evidence EBV-LMP1regulate glucose metabolism in tumor cells by the transcription factor c-Myc.Fatty acid metabolism also play a pivotal role in the carcinogenesis process. Recent studies have found that the tumor cells showed abnormal activation of fatty acid (3oxidation state can promote tumor cell proliferation and survival under conditions of metabolic stress, while maintaining the tumor cells against apoptosis. The carnitine palmitoyl transferase (CPT) in fatty acid β-oxidation direct regulates carnitine shuttle mechanism and fatty acid β-oxidation, abnormal activation of the key rate-limiting enzyme--CPT in the fatty acid β-oxidation may reflect its meat alkali shuttle function. And prompts CPT1molecules may have a potential therapeutic target for tumor targeting. The second part of this subject we use metabolomics lipid metabolism as the breakthrough point, analysis of nasopharyngeal carcinoma cells through metabolomics, oil red O staining, seahorse metabolic analysis system and immunohistochemical method to clear the fatty acids in nasopharyngeal carcinoma cells beta oxidation in abnormal activation of the state, discovered the carnitine palmitoyl transferase CPT1A is mediated nasopharyngeal carcinoma cell fatty acid oxidation of beta key molecules, high CPT1A expression is associated with nasopharyngeal carcinoma cell proliferation malignant phenotype.The above study were discussed the mechanism of NPC cell energy metabolism changes from glucose metabolism and fatty acid β oxidation, enriched our energy metabolism in tumor cells reprogrammed understanding from the perspective of cellular metabolism reprogramming the development of new targeted prevention, treatment and diagnosis of a new experimental basis.