Gupta Vibhor, Wellen Kathryn E, Mazurek Sybille, Bamezai Rameshwar N K
Nal Centre of Applied Human Genetics, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
Curr Pharm Des. 2014;20(15):2595-606. doi: 10.2174/13816128113199990484.
Cancer cells are characterized by reprogramming of energy metabolism. Over the last decade, understanding of the metabolic changes that occur in cancer has increased dramatically, with great interest in targeting metabolism for cancer therapy. Pyruvate kinase isoenzyme type M2 (abbreviations: PKM2, M2-PK) plays a key role in modulating glucose metabolism to support cell proliferation. PKM2, like other PK isoforms, catalyzes the last energy-generating step in glycolysis, but is unique in its capacity to be regulated. PKM2 is regulated at several cellular levels, including gene expression, alternative splicing and post-translational modification. In addition, PKM2 is regulated by key metabolic intermediates and interacts with more than twenty different proteins. Hence, this isoenzyme is an important regulator of glycolysis, and additionally functions in other novel roles that have recently emerged. Recent evidence indicates that intervening with the complex regulatory network of PKM2 has severe consequences on tumor cell proliferation, indicating the potential of this enzyme as a target for tumor therapy.
癌细胞的特征是能量代谢重编程。在过去十年中，人们对癌症中发生的代谢变化的理解有了显著增加，对将代谢作为癌症治疗靶点也产生了浓厚兴趣。丙酮酸激酶M2型同工酶（缩写：PKM2，M2-PK）在调节葡萄糖代谢以支持细胞增殖方面起关键作用。PKM2与其他PK同工型一样，催化糖酵解的最后一个产生能量的步骤，但其独特之处在于其可被调节的能力。PKM2在多个细胞水平受到调节，包括基因表达、可变剪接和翻译后修饰。此外，PKM2受关键代谢中间产物调节，并与二十多种不同蛋白质相互作用。因此，这种同工酶是糖酵解的重要调节因子，此外还在最近出现的其他新功能中发挥作用。最近的证据表明，干预PKM2的复杂调节网络会对肿瘤细胞增殖产生严重影响，这表明该酶作为肿瘤治疗靶点的潜力。
