M2型丙酮酸激酶在肿瘤代谢重编程中的作用研究进展  

Research progress on the role of M2 type pyruvate kinase glycolipid metabolism key enzymes in metabolic reprogramming of malignant tumors

作　　者：陈烨凯 李和根[1] 赵天成[2] 朱丽华[1] 周蕾[1] Chen Yekai;Li Hegen;Zhao Tiancheng;Zhu Lihua;Zhou Lei(Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China;Shanghai 6th People′s Hospital,Shanghai 200032,China)

机构地区：[1]上海中医药大学附属龙华医院肿瘤三科,上海200032 [2]上海市第六人民医院胸外科,上海200032

出　　处：《肿瘤代谢与营养电子杂志》2024年第4期571-575,共5页Electronic Journal of Metabolism and Nutrition of Cancer

基　　金：国家自然科学基金(82374532,82205214);上海市2021年度“科技创新行动计划”医学创新研究专项项目(21MC1930500);上海市名老中医学术经验研究工作室建设项目(SHGZS-202215)。

摘　　要：代谢重编程是肿瘤的重要特征之一,其为肿瘤细胞提供三磷酸腺苷(ATP)、细胞内蛋白质及核苷酸生物合成提供必需的大分子,从而促进肿瘤细胞的增殖和存活。肿瘤细胞的新陈代谢与正常细胞有较大差异,肿瘤的可塑性强是导致靶向肿瘤代谢治疗研究进展缓慢的重要原因。糖脂代谢关键代谢酶可通过多种方式改变自身活性,获得非代谢酶功能,从而驱动肿瘤细胞的代谢重编程。这些方式主要包括蛋白质自身异常表达、突变,蛋白质翻译后修饰改变,寡聚状态变化及亚细胞定位的易位等。丙酮酸激酶(PK)是细胞糖酵解通路的关键酶,可催化磷酸烯醇丙酮酸转化为丙酮酸并产生三磷酸腺苷。M2型丙酮酸激酶(PKM2)可以通过增强Warburg效应来促进肿瘤细胞的增殖和合成代谢,还能够进入细胞核内作为共转录因子和蛋白激酶调节基因转录,在恶性肿瘤代谢重塑、细胞增殖和转移过程中发挥着重要作用。本文通过总结PKM2在多种肿瘤类型中的异常表达情况、在肿瘤代谢调控中的作用和机制及在中药领域的应用和突破,以期为临床肿瘤代谢治疗提供新的思路。Metabolic reprogramming is one of the important features of tumors,which provides essential macromolecules for adenosine triphosphate(ATP)and intracellular protein and nucleotide biosynthesis,thereby promoting the proliferation and survival of tumor cells.The metabolism of tumor cells is significantly different from that of normal cells,and the strong plasticity of tumors is an important reason for the slow progress of targeted tumor metabolic therapy research.Research has shown that key metabolic enzymes in glucose and lipid metabolism can alter their own activity and obtain non metabolic enzyme functions in various ways,thereby driving metabolic reprogramming in tumor cells.These methods mainly include abnormal protein expression,mutations,post-translational modifications,changes in oligomeric state,and subcellular translocation.Pyruvate kinase is a key enzyme in the cellular glycolytic pathway,which catalyzes the conversion of phosphoenolpyruvate to pyruvate and produces adenosine triphosphate.M2 type pyruvate kinase(PKM2)can promote tumor cell proliferation and synthetic metabolism by enhancing the Warburg effect.It can also enter the nucleus as a co transcription factor and protein kinase to regulate gene transcription,playing an important role in malignant tumor metabolic remodeling,cell proliferation,and metastasis.This article summarizes the abnormal expression of PKM2 in various types of tumors,its role and mechanism in tumor metabolism regulation,and its application and breakthroughs in the field of traditional Chinese medicine,in order to provide new ideas for clinical tumor metabolism therapy.

关 键 词：M2型丙酮酸激酶 肿瘤代谢重编程 Warburg效应 糖脂代谢 代谢酶 三磷酸腺苷 增殖 转录 

分 类 号：R730.2[医药卫生—肿瘤]