The double-edged sword of AMPK signaling in cancer and its therapeutic implications.
The double-edged sword of AMPK signaling in cancer and its therapeutic implications.
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DOI：
10.1007/s12272-015-0549-z
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发表时间：
2015-03
影响因子：
6.7
通讯作者：
Hay N
中科院分区：
文献类型：
--
作者：
Jeon SM;Hay N
5′-AMP活化蛋白激酶（AMPK）在各种代谢应激条件下维持能量和氧化还原稳态中起着关键作用。在代谢应激过程中，AMPK的激活可以触发代谢适应，这是通过维持ATP和NADPH水平来维持细胞存活的关键过程。这种基本过程调节的重要性使得AMPK信号通路成为许多病理学如糖尿病和癌症中最有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的作用不会被简单地定义为抗肿瘤或促肿瘤，但它似乎有两个面孔，就像一把双刃剑。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的抗肿瘤作用不依赖于AMPK;而是AMPK的激活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，我们总结和讨论了最近的研究结果表明，在癌症中的两个方面的AMPK，并讨论了我们如何可以利用这种独特的功能AMPK的新的治疗干预。
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.
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影响因子：
29
作者：
Gowans GJ;Hawley SA;Ross FA;Hardie DG
通讯作者：
Hardie DG
影响因子：
50.3
作者：
Carretero J;Shimamura T;Rikova K;Jackson AL;Wilkerson MD;Borgman CL;Buttarazzi MS;Sanofsky BA;McNamara KL;Brandstetter KA;Walton ZE;Gu TL;Silva JC;Crosby K;Shapiro GI;Maira SM;Ji H;Castrillon DH;Kim CF;García-Echeverría C;Bardeesy N;Sharpless NE;Hayes ND;Kim WY;Engelman JA;Wong KK
通讯作者：
Wong KK
苯甲曲作为预防和乳腺癌异种移植的治疗。
影响因子：
8.8
作者：
Appleyard, M. V. C. L.;Murray, K. E.;Coates, P. J.;Wullschleger, S.;Bray, S. E.;Kernohan, N. M.;Fleming, S.;Alessi, D. R.;Thompson, A. M.
通讯作者：
Thompson, A. M.
影响因子：
5.9
作者：
Dupuy F;Griss T;Blagih J;Bridon G;Avizonis D;Ling C;Dong Z;Siwak DR;Annis MG;Mills GB;Muller WJ;Siegel PM;Jones RG
通讯作者：
Jones RG
影响因子：
3.5
作者：
CARLING, D;ZAMMIT, VA;HARDIE, DG
通讯作者：
HARDIE, DG