Jeon Sang-Min, Hay Nissim
College of Pharmacy, Ajou University, Suwon, Gyeonggi-do, 443-749, Republic of Korea,
Arch Pharm Res. 2015 Mar;38(3):346-57. doi: 10.1007/s12272-015-0549-z. Epub 2015 Jan 10.
5'-AMP-activated protein kinase (AMPK) plays a pivotal role in maintaining energy and redox homeostasis under various metabolic stress conditions. Metabolic adaptation, which can be triggered by the activation of AMPK during metabolic stress, is the critical process for cell survival through the maintenance of ATP and NADPH levels. The importance of such regulation of fundamental process poses the AMPK signaling pathway in one of the most attractive therapeutic targets in many pathologies such as diabetes and cancer. In cancer, however, accumulating data suggest that the role of AMPK would not be simply defined as anti- or pro-tumorigenic, but it seems to have two faces like a double-edged sword. Importantly, recent studies showed that the anti-tumorigenic effects of many 'indirect' AMPK activators such as anti-diabetic biguanides are not dependent on AMPK; rather the activation of AMPK induces the resistance to their cytotoxic effects, emphasizing the pro-tumorigenic effect of AMPK. In this review, we summarize and discuss recent findings suggesting the two faces of AMPK in cancer, and discuss how we can exploit this unique feature of AMPK for novel therapeutic intervention.
5'-单磷酸腺苷激活蛋白激酶（AMPK）在各种代谢应激条件下维持能量和氧化还原稳态方面发挥着关键作用。代谢适应是细胞在代谢应激期间通过激活AMPK触发的，是通过维持ATP和NADPH水平实现细胞存活的关键过程。这种对基本过程的调节的重要性使AMPK信号通路成为糖尿病和癌症等许多疾病中最具吸引力的治疗靶点之一。然而，在癌症中，越来越多的数据表明，AMPK的作用不能简单地定义为抗肿瘤或促肿瘤，它似乎像一把双刃剑一样有两面性。重要的是，最近的研究表明，许多“间接”AMPK激活剂（如抗糖尿病双胍类药物）的抗肿瘤作用并不依赖于AMPK；相反，AMPK的激活会诱导对其细胞毒性作用的抗性，强调了AMPK的促肿瘤作用。在这篇综述中，我们总结并讨论了最近表明AMPK在癌症中有两面性的研究结果，并讨论了如何利用AMPK的这一独特特性进行新的治疗干预。
