期刊
CANCER CELL
卷 23, 期 6, 页码 839-852出版社
CELL PRESS
DOI: 10.1016/j.ccr.2013.04.008
关键词
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资金
- Case Comprehensive Cancer Center [P30CA043703]
- Korea Healthcare Technology R&D Project, Ministry for Health & Welfare Affairs, Republic of Korea [A092255]
- Samsung Medical Center [GFO1130011]
- [R01 NS082312]
- Korea Health Promotion Institute [A092255] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Council of Science & Technology (NST), Republic of Korea [2E23730] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Glioblastoma multiforme (GBM) displays cellular hierarchies harboring a subpopulation of stem-like cells (GSCs). Enhancer of Zeste Homo log 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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