AMPK: a contextual oncogene or tumor suppressor?
AMPK: a contextual oncogene or tumor suppressor?
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DOI：
10.1158/0008-5472.can-12-3876
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发表时间：
2013-05-15
期刊：
影响因子：
11.2
通讯作者：
Mills GB
中科院分区：
文献类型：
--
作者：
Liang J;Mills GB
AMP 激活蛋白激酶 (AMPK) 的作用是在细胞和有机体水平上监测和维持能量稳态。 AMPK 历史上主要被认为是 TSC1/2/mTOR 通路上游 LKB1/STK11 肿瘤抑制因子（LKB1 突变导致 Peutz Jegher 癌症易感综合征，PJS）级联的一个组成部分，因此可能是肿瘤抑制因子。然而，最近已证明 AMPK 在面对包括生物能、生长因子和癌基因应激在内的外在和内在应激源时可促进癌细胞存活，这与表明 AMPK 是致癌转化所必需的研究相一致。因此，AMPK 是否充当真正的肿瘤抑制基因或背景癌基因，特别重要的是，在癌症治疗期间 AMPK 是否应该被靶向激活或抑制，这是有争议的，需要澄清。我们的目标是通过回顾 AMPK 的作用来启动对这些关键问题的讨论，重点是癌细胞对微环境压力的适应和治疗干预。总体 AMPK 功能是几篇综合评论的主题。
The AMP-activated protein kinase (AMPK) functions to monitor and maintain energy homeostasis at the cellular and organismal level. AMPK was perceived historically primarily as a component of the LKB1/STK11 tumor suppressor (LKB1 mutations cause the Peutz Jegher’s cancer predisposition syndrome, PJS) cascade upstream of the TSC1/2/mTOR pathway and thus likely to be a tumor suppressor. However, AMPK has recently been demonstrated to promote cancer cell survival in the face of extrinsic and intrinsic stressors including bioenergetic, growth factor and oncogene stress, compatible with studies showing that AMPK is required for oncogenic transformation. Thus whether AMPK acts as a bona fide tumor suppressor or a contextual oncogene and, of particular importance, whether AMPK should be targeted for activation or inhibition during cancer therapy is controversial and requires clarification. We aim to initiate discussions of these critical questions by reviewing the role of AMPK with an emphasis on cancer cell adaptation to microenvironment stress and therapeutic intervention. Overall AMPK function is the topic of several comprehensive reviews.