PMID- 23684459
OWN - NLM
STAT- MEDLINE
DCOM- 20130823
LR  - 20220311
IS  - 1878-3686 (Electronic)
IS  - 1535-6108 (Print)
IS  - 1535-6108 (Linking)
VI  - 23
IP  - 6
DP  - 2013 Jun 10
TI  - Phosphorylation of EZH2 activates STAT3 signaling via STAT3 methylation and 
      promotes tumorigenicity of glioblastoma stem-like cells.
PG  - 839-52
LID - S1535-6108(13)00177-3 [pii]
LID - 10.1016/j.ccr.2013.04.008 [doi]
AB  - 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.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Kim, Eunhee
AU  - Kim E
AD  - Department of Stem Cell Biology and Regenerative Medicine, Lerner Research 
      Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
FAU - Kim, Misuk
AU  - Kim M
FAU - Woo, Dong-Hun
AU  - Woo DH
FAU - Shin, Yongjae
AU  - Shin Y
FAU - Shin, Jihye
AU  - Shin J
FAU - Chang, Nakho
AU  - Chang N
FAU - Oh, Young Taek
AU  - Oh YT
FAU - Kim, Hong
AU  - Kim H
FAU - Rheey, Jingeun
AU  - Rheey J
FAU - Nakano, Ichiro
AU  - Nakano I
FAU - Lee, Cheolju
AU  - Lee C
FAU - Joo, Kyeung Min
AU  - Joo KM
FAU - Rich, Jeremy N
AU  - Rich JN
FAU - Nam, Do-Hyun
AU  - Nam DH
FAU - Lee, Jeongwu
AU  - Lee J
LA  - eng
GR  - R01 NS083767/NS/NINDS NIH HHS/United States
GR  - P30 CA043703/CA/NCI NIH HHS/United States
GR  - P01 CA163205/CA/NCI NIH HHS/United States
GR  - R01 NS082312/NS/NINDS NIH HHS/United States
GR  - P30CA043703/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130516
PL  - United States
TA  - Cancer Cell
JT  - Cancer cell
JID - 101130617
RN  - 0 (Polycomb-Group Proteins)
RN  - 0 (STAT3 Transcription Factor)
RN  - EC 2.1.1.43 (EZH2 protein, human)
RN  - EC 2.1.1.43 (Enhancer of Zeste Homolog 2 Protein)
RN  - EC 2.1.1.43 (Polycomb Repressive Complex 2)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
CIN - Cancer Cell. 2013 Jun 10;23(6):711-3. PMID: 23763996
MH  - Animals
MH  - Cell Transformation, Neoplastic
MH  - Enhancer of Zeste Homolog 2 Protein
MH  - Gene Silencing
MH  - Glioblastoma/*metabolism/pathology
MH  - Humans
MH  - Methylation
MH  - Mice
MH  - Phosphorylation
MH  - Polycomb Repressive Complex 2/metabolism/*physiology
MH  - Polycomb-Group Proteins
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - STAT3 Transcription Factor/*metabolism
MH  - Signal Transduction
MH  - Transplantation, Heterologous
MH  - Tumor Cells, Cultured
PMC - PMC4109796
MID - NIHMS587199
EDAT- 2013/05/21 06:00
MHDA- 2013/08/24 06:00
PMCR- 2014/07/24
CRDT- 2013/05/21 06:00
PHST- 2012/07/16 00:00 [received]
PHST- 2013/02/02 00:00 [revised]
PHST- 2013/04/08 00:00 [accepted]
PHST- 2013/05/21 06:00 [entrez]
PHST- 2013/05/21 06:00 [pubmed]
PHST- 2013/08/24 06:00 [medline]
PHST- 2014/07/24 00:00 [pmc-release]
AID - S1535-6108(13)00177-3 [pii]
AID - 10.1016/j.ccr.2013.04.008 [doi]
PST - ppublish
SO  - Cancer Cell. 2013 Jun 10;23(6):839-52. doi: 10.1016/j.ccr.2013.04.008. Epub 2013 
      May 16.