AMPK modulates Hippo pathway activity to regulate energy homeostasis.
AMPK modulates Hippo pathway activity to regulate energy homeostasis.
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DOI：
10.1038/ncb3113
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发表时间：
2015-04
影响因子：
21.3
通讯作者：
中科院分区：
文献类型：
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Hippo通路被发现是一个保守的肿瘤抑制通路，限制细胞增殖和凋亡。然而，在器官大小控制和癌症预防的背景下，调节Hippo通路的上游信号在很大程度上是未知的。在这里，我们报道葡萄糖，用于ATP生成的普遍能量来源，调节Hippo通路下游效应物YAP。我们发现Hippo通路和amp激活的蛋白激酶（AMPK）在葡萄糖饥饿期间都被激活，导致YAP磷酸化并导致其失活。我们还发现葡萄糖转运蛋白3 （GLUT3）是一个参与葡萄糖代谢的yap调控基因。总之，这些结果表明，葡萄糖介导的能量稳态是参与Hippo通路调控的上游事件，并且可能是YAP促进糖酵解的致癌功能，从而提供了葡萄糖代谢与Hippo通路在组织维持和癌症预防中的令人兴奋的联系。
The Hippo pathway was discovered as a conserved tumour suppressor pathway restricting cell proliferation and apoptosis. However, the upstream signals that regulate the Hippo pathway in the context of organ size control and cancer prevention are largely unknown. Here, we report that glucose, the ubiquitous energy source utilised for ATP generation, regulates the Hippo pathway downstream effector YAP. We show that both the Hippo pathway and AMP-activated protein kinase (AMPK) were activated during glucose starvation, resulting in phosphorylation of YAP and contributing to its inactivation. We also identified glucose-transporter 3 (GLUT3) as a YAP-regulated gene involved in glucose metabolism. Together, these results demonstrate that glucose-mediated energy homeostasis is an upstream event involved in regulation of the Hippo pathway and, potentially, an oncogenic function of YAP in promoting glycolysis, thereby providing an exciting link between glucose metabolism and the Hippo pathway in tissue maintenance and cancer prevention.
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