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。
Abstract
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
Key words
M2 type pyruvate kinase /
Tumor metabolism reprogramming /
Warburg effect /
Glycolipid metabolism /
Metabolic enzymes /
Adenosine triphosphate /
Proliferation /
Transcribe
1陈烨凯,1李和根,2赵天成,1朱丽华,1周 蕾.
M2 型丙酮酸激酶在肿瘤代谢重编程中的作用研究进展[J]. 肿瘤代谢与营养电子杂志. 2024, 11(4): 571-575
1Chen Yekai,1Li Hegen,2Zhao Tiancheng,1Zhu Lihua,1Zhou Lei.
Research progress on the role of M2 type pyruvate kinase glycolipid metabolism key enzymes in metabolic reprogramming of
malignant tumors[J]. Electronic Journal of Metabolism and Nutrition of Cancer. 2024, 11(4): 571-575
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
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)