한빛사 논문
Abstract
Eunhee Kim,1,6 Misuk Kim,2,6 Dong-Hun Woo,1,6 Yongjae Shin,1 Jihye Shin,3 Nakho Chang,2 Young Taek Oh,2 Hong Kim,1 Jingeun Rheey,2 Ichiro Nakano,4 Cheolju Lee,3 Kyeung Min Joo,5 Jeremy N. Rich,1 Do-Hyun Nam,2,* and Jeongwu Lee1,*
1 Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
2 Department of Neurosurgery and Samsung Advanced Institute for Health Sciences and Technology, Samsung Medical Center,
Sungkyunkwan University School of Medicine, Seoul, 135-710, Korea
3 BRI, Life Sciences Division, Korea Institute of Science and Technology, Seoul 136-791, Korea
4 Department of Neurological Surgery, Center for Neuro-oncology, James Cancer Hospital and The Ohio State University, Columbus,
OH 43210, USA
5 Department of Anatomy and Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi-do, 440-746, Korea
6 These authors contributed equally to this work
*Correspondence: Do-Hyun Nam, Jeongwu Lee
Summary
Glioblastoma multiforme (GBM) displays cellular hierarchies harboring a subpopulation of stem-like cells (GSCs). Enhancer of Zeste Homolog 2 (EZH2), the lysine methyltransferase of Polycomb repressive complex 2, mediates transcriptional repression of prodifferentiation genes in both normal and neoplastic stem cells. An oncogenic role of EZH2 as a transcriptional silencer is well established; however, additional functions of EZH2 are incompletely understood. Here, we show that EZH2 binds to and methylates STAT3, leading to enhanced STAT3 activity by increased tyrosine phosphorylation of STAT3. The EZH2-STAT3 interaction preferentially occurs in GSCs relative to non-stem bulk tumor cells, and it requires a specific phosphorylation of EZH2. Inhibition of EZH2 reverses the silencing of Polycomb target genes and diminishes STAT3 activity, suggesting therapeutic strategies.
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