EZH2 promotes metabolic reprogramming in glioblastomas through epigenetic repression of EAF2-HIF1α signaling.
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.
Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China.
Bo
B
Pang
Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, Shandong, China.
Xiang-Rong
XR
Zheng
Department of Gynecology and Obstetrics, Jinan Central Hospital affiliated to Shandong University, Jinan, 250013, Shandong, China.
Jing-Xia
JX
Tian
Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, Shandong, China.
Tai-Hong
TH
Gao
Department of Histology and Embryology, Shandong University School of Medicine, Jinan, 250012, Shandong, China.
Guang-Yan
GY
Gu
Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, Shandong, China.
Rui
R
Zhang
Department of Gynecology and Obstetrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, Shandong, China.
Yi-Bing
YB
Fu
Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, Shandong, China.
Qi
Q
Pang
Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China.
Xin-Gang
XG
Li
Department of Histology and Embryology, Shandong University School of Medicine, Jinan, 250012, Shandong, China.
Qian
Q
Liu
D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000502:physiology*; D063185:Epigenetic Repression; D005909:Glioblastoma / Q000209:etiology* / Q000378:metabolism; D005910:Glioma / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*
C472771:EAF2 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein
EAF2; EZH2; HIF1α; Warburg effect; glioblastoma