EZH2 promotes metabolic reprogramming in glioblastomas through epigenetic repression of EAF2-HIF1α signaling

// Bo Pang 1, * , Xiang-Rong Zheng 2, * , Jing-xia Tian 3 , Tai-hong Gao 2 , Guang-yan Gu 4 , Rui Zhang 2 , Yi-Bing Fu 5 , Qi Pang 2 , Xin-Gang Li 1 , Qian Liu 4 1 Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China 2 Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, Shandong, China 3 Department of Gynecology and Obstetrics, Jinan Central Hospital affiliated to Shandong University, Jinan, 250013, Shandong, China 4 Department of Histology and Embryology, Shandong University School of Medicine, Jinan, 250012, Shandong, China 5 Department of Gynecology and Obstetrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, Shandong, China * These authors contributed equally to this work Correspondence to: Qian Liu, email: cardioqian@126.com Xin-Gang Li, email: lixingang1959@163.com Keywords: EZH2, glioblastoma, Warburg effect, HIF1α, EAF2 Received: October 18, 2015      Accepted: May 13, 2016      Published: June 01, 2016 ABSTRACT 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.