线粒体磷酸烯醇式丙酮酸羧激酶与肿瘤

Mitochondrial phosphoenolpyruvate carboxykinase in human cancer

线粒体磷酸烯醇式丙酮酸羧激酶(mitochondrial phosphoenolpyruvate carboxykinase, PCK2)是糖异生途径中的关键限速酶,参与甘油、氨基酸和核苷酸合成以及三羧酸(tricarboxylic acid, TCA)循环中未被氧化的氨基酸碳骨架的流失反应(cataplerosis)。PCK2是连接TCA循环、糖酵解和糖异生的枢纽分子,动态调节细胞内的合成代谢以提供足够的能量和代谢中间体。PCK2通过促进TCA循环中的碳流动和糖异生作用供给细胞能量和物质,还能通过糖酵解促进Warburg效应。在不同肿瘤中PCK2的作用不同,在肝癌中PCK2具有抑癌作用,在大部分非糖异生器官来源的肿瘤中,PCK2具有促癌作用。PCK2还参与肿瘤微环境中的糖脂代谢重塑,在肿瘤细胞代谢重编程中扮演重要角色。该文综述了近年PCK2在肿瘤中的研究进展。

Mitochondrial phosphoenolpyruvate carboxykinase(PCK2)is a key rate-limiting enzyme in gluconeogenesis,which is involved in the synthesis of glycerol,amino acids and nucleotides as well as the cataplerosis of the unoxidized carbon skeletons of amino acids in the tricarboxylic acid(TCA)cycle.PCK2 is a pivotal molecule that connects TCA cycle,glycolysis and gluconeogenesis,and dynamically regulates intracellular anabolism to provide sufficient energy and metabolic intermediates.PCK2 can supply energy and substances to cells through promoting the carbon flow of the TCA cycle and gluconeogenesis,and promote the Warburg effect through glycolysis.The roles of PCK2 are different in various tumors.It has an anti-tumor effect in liver cancer,but it has a cancer-promoting effect in most tumors derived from non-gluconeogenic organs.PCK2 participates in the remodeling of glucose and lipid metabolism in tumor microenvironment and plays an important role in the metabolic reprogramming of tumor cells.This paper summarized the research progress of PCK2 in tumor in recent years.