M2型丙酮酸激酶非代谢功能在肿瘤治疗中的研究进展

Research progress of nonmetabolic function of M2-pyruvate kinase in tumor therapy

丙酮酸激酶(pyruvate kinase,PK),作为糖酵解的关键酶之一,可以编码四个不同亚型的基因,其中M2型丙酮酸激酶(PKM2)主要表达在正常人类胚胎发育中,和组织修复、再生密切相关,随着研究的深入,PKM2在肿瘤组织中的作用受到越来越多的关注。PKM2除了代谢作用外,还可以通过PKM2抑制剂和激活剂变构调节四聚体和二聚体,二聚体状态的PKM2可以调节细胞核中的基因表达及细胞增殖。本文综述了PKM2表达调控,重点介绍了PKM2非代谢功能及在抗肿瘤治疗中的临床应用。

Pyruvate kinase(PK),as one of the key enzymes of glycolysis,can encode genes of four different subtypes,among which the M2-type pyruvate kinase(PKM2)is mainly expressed in normal human embryonic development and is closely related to tissue repair and regeneration.With the deepening of research,the role of PKM2 in tumor tissues has attracted more and more attention.In addition to metabolism,PKM2 can also allosterically regulate tetramers and dimers through PKM2 inhibitors and activators.In the dimer state,PKM2 can regulate gene expression and cell proliferation in the nucleus.This paper reviews the regulation of PKM2 expression,with emphasis on the non-metabolic function of PKM2 and its clinical application in antitumor therapy.