Wang Wenqi, Xiao Zhen-Dong, Li Xu, Aziz Kathryn E, Gan Boyi, Johnson Randy L, Chen Junjie
Department of Experimental Radiation Oncology, 1515 Holcombe Boulevard Houston, Texas 77030, USA.
1] Department of Experimental Radiation Oncology, 1515 Holcombe Boulevard Houston, Texas 77030, USA [2] Cancer Biology Program, The University of Texas Graduate School of Biomedical Science, 1515 Holcombe Boulevard Houston, Texas 77030, USA.
Nat Cell Biol. 2015 Apr;17(4):490-9. doi: 10.1038/ncb3113. Epub 2015 Mar 9.
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 used 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.
河马通路作为一种保守的肿瘤抑制通路被发现，可限制细胞增殖和凋亡。然而，在器官大小控制和癌症预防背景下调节河马通路的上游信号在很大程度上尚不清楚。在此，我们报告称，葡萄糖这种用于生成三磷酸腺苷（ATP）的普遍能量来源，可调节河马通路的下游效应因子Yes相关蛋白（YAP）。我们发现，在葡萄糖饥饿期间，河马通路和腺苷酸活化蛋白激酶（AMPK）均被激活，导致YAP磷酸化并促使其失活。我们还确定葡萄糖转运蛋白3（GLUT3）是一个受YAP调节的参与葡萄糖代谢的基因。这些结果共同表明，葡萄糖介导的能量稳态是调节河马通路的上游事件，并且可能是YAP在促进糖酵解方面的致癌功能，从而在组织维持和癌症预防中提供了葡萄糖代谢与河马通路之间令人兴奋的联系。
