摘要
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。丙酮酸激酶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,在肿瘤的发生发展中发挥重要作用。本文重点介绍了PKM2在Warburg效应、合成代谢和肿瘤微环境方面的新突破,并简要介绍了PKM2的非代谢功能以及PKM2靶向小分子药物临床转化的最新进展,以期为治疗肿瘤提供新的思路。
The metabolism of cancer cells is quite different from that of normal cells,and the strong plasticity of cancer has resulted in slow progress in the field of targeting cancer metabolism therapy.Pyruvate kinase is a key enzyme in the cellular glycolytic pathway,catalyzing the conversion of phosphoenolpyruvate to pyruvate and the production of adenosine triphosphate.pyruvate kinase M2 isozyme(PKM2)not only can promote cancer cell proliferation and anabolism by enhancing the Warburg effect,but also can translocate to nucleus as a co-transcription factor and protein kinase to regulate gene transcription,playing an important role in tumorigenesis and development.This review focuses on the new breakthroughs of PKM2 on the Warburg effect,anabolism and tumor microenvironment,and briefly introduces the non-metabolic function of PKM2 and the latest progress in the clinical translation of PKM2-targeting small molecule drugs,providing new ideas for tumor therapy.
作者
李朵
肖迪
楚菲依
杨小平
LI Duo;XIAO Di;CHU Feiyi;YANG Xiaoping(Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province,School of Medicine,Hunan Normal University,Changsha,410013,Hunan,China)
出处
《肿瘤药学》
CAS
2022年第3期303-311,共9页
Anti-Tumor Pharmacy
基金
国家自然科学基金面上项目(82172653、81874212)
湖南省自然科学基金青年项目(2021JJ40369)
晓庄学院医学院开放课题基金项目(KF2021017、KF2022001)。
