Pang Bo, Zheng Xiang-Rong, Tian Jing-Xia, Gao Tai-Hong, Gu Guang-Yan, Zhang Rui, Fu Yi-Bing, Pang Qi, Li Xin-Gang, Liu Qian
Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China.
Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, Shandong, China.
Oncotarget. 2016 Jul 19;7(29):45134-45143. doi: 10.18632/oncotarget.9761.
Cancer cells prefer glycolysis for energy metabolism, even when there is sufficient oxygen to make it unnecessary. This is called the Warburg effect, and it promotes tumorigenesis and malignant progression. In this study, we demonstrated that EZH2, a multifaceted oncogenic protein involved in tumor proliferation, invasion and metastasis, promotes glioblastoma tumorigenesis and malignant progression through activation of the Warburg effect. We observed that HIF1α is a target of EZH2 whose activation is necessary for EZH2-mediated metabolic adaption, and that HIF1α is activated upon EZH2 overexpression. EZH2 suppressed expression of EAF2, which in turn upregulated HIF1α levels. We conclude from these results that EZH2 promotes tumorigenesis and malignant progression in part by activating glycolysis through an EAF2-HIF1α signaling axis.
癌细胞即使在有足够氧气使其无需进行糖酵解的情况下，仍倾向于通过糖酵解进行能量代谢。这被称为瓦伯格效应，它会促进肿瘤发生和恶性进展。在本研究中，我们证明了EZH2（一种参与肿瘤增殖、侵袭和转移的多面致癌蛋白）通过激活瓦伯格效应促进胶质母细胞瘤的肿瘤发生和恶性进展。我们观察到HIF1α是EZH2的一个靶点，其激活对于EZH2介导的代谢适应是必需的，并且在EZH2过表达时HIF1α被激活。EZH2抑制EAF2的表达，进而上调HIF1α水平。我们从这些结果得出结论，EZH2部分通过EAF2-HIF1α信号轴激活糖酵解来促进肿瘤发生和恶性进展。
