Research Papers:

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

Bo Pang, Xiang-Rong Zheng, Jing-xia Tian, Tai-hong Gao, Guang-yan Gu, Rui Zhang, Yi-Bing Fu, Qi Pang, Xin-Gang Li and Qian Liu _

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Oncotarget. 2016; 7:45134-45143. https://doi.org/10.18632/oncotarget.9761

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Bo Pang1,*, Xiang-Rong Zheng2,*, Jing-xia Tian3, Tai-hong Gao2, Guang-yan Gu4, Rui Zhang2, Yi-Bing Fu5, Qi Pang2, Xin-Gang Li1, Qian Liu4

1Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China

2Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, Shandong, China

3Department of Gynecology and Obstetrics, Jinan Central Hospital affiliated to Shandong University, Jinan, 250013, Shandong, China

4Department of Histology and Embryology, Shandong University School of Medicine, Jinan, 250012, Shandong, China

5Department 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: [email protected]

Xin-Gang Li, email: [email protected]

Keywords: EZH2, glioblastoma, Warburg effect, HIF1α, EAF2

Received: October 18, 2015     Accepted: May 13, 2016     Published: June 01, 2016


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.

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