PMID- 19934320
OWN - NLM
STAT- MEDLINE
DCOM- 20100105
LR  - 20220311
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Linking)
VI  - 69
IP  - 24
DP  - 2009 Dec 15
TI  - EZH2 is essential for glioblastoma cancer stem cell maintenance.
PG  - 9211-8
LID - 10.1158/0008-5472.CAN-09-1622 [doi]
AB  - Overexpression of the polycomb group protein enhancer of zeste homologue 2 (EZH2) 
      occurs in diverse malignancies, including prostate cancer, breast cancer, and 
      glioblastoma multiforme (GBM). Based on its ability to modulate transcription of 
      key genes implicated in cell cycle control, DNA repair, and cell differentiation, 
      EZH2 is believed to play a crucial role in tissue-specific stem cell maintenance 
      and tumor development. Here, we show that targeted pharmacologic disruption of 
      EZH2 by the S-adenosylhomocysteine hydrolase inhibitor 3-deazaneplanocin A 
      (DZNep), or its specific downregulation by short hairpin RNA (shRNA), strongly 
      impairs GBM cancer stem cell (CSC) self-renewal in vitro and tumor-initiating 
      capacity in vivo. Using genome-wide expression analysis of DZNep-treated GBM 
      CSCs, we found the expression of c-myc, recently reported to be essential for GBM 
      CSCs, to be strongly repressed upon EZH2 depletion. Specific shRNA-mediated 
      downregulation of EZH2 in combination with chromatin immunoprecipitation 
      experiments revealed that c-myc is a direct target of EZH2 in GBM CSCs. Taken 
      together, our observations provide evidence that direct transcriptional 
      regulation of c-myc by EZH2 may constitute a novel mechanism underlying GBM CSC 
      maintenance and suggest that EZH2 may be a valuable new therapeutic target for 
      GBM management.
FAU - Suva, Mario-Luca
AU  - Suva ML
AD  - Division of Experimental Pathology, Institute of Pathology, University of 
      Lausanne, Lausanne, Switzerland.
FAU - Riggi, Nicolo
AU  - Riggi N
FAU - Janiszewska, Michalina
AU  - Janiszewska M
FAU - Radovanovic, Ivan
AU  - Radovanovic I
FAU - Provero, Paolo
AU  - Provero P
FAU - Stehle, Jean-Christophe
AU  - Stehle JC
FAU - Baumer, Karine
AU  - Baumer K
FAU - Le Bitoux, Marie-Aude
AU  - Le Bitoux MA
FAU - Marino, Denis
AU  - Marino D
FAU - Cironi, Luisa
AU  - Cironi L
FAU - Marquez, Victor E
AU  - Marquez VE
FAU - Clement, Virginie
AU  - Clement V
FAU - Stamenkovic, Ivan
AU  - Stamenkovic I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Transcription Factors)
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)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - DNA-Binding Proteins/antagonists & inhibitors/*biosynthesis/genetics
MH  - Down-Regulation
MH  - Enhancer of Zeste Homolog 2 Protein
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic
MH  - Genes, myc
MH  - Glioblastoma/genetics/metabolism/*pathology
MH  - Humans
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Neoplastic Stem Cells/metabolism/*pathology
MH  - Polycomb Repressive Complex 2
MH  - RNA, Small Interfering/genetics
MH  - Transcription Factors/antagonists & inhibitors/*biosynthesis/genetics
EDAT- 2009/11/26 06:00
MHDA- 2010/01/06 06:00
CRDT- 2009/11/26 06:00
PHST- 2009/11/26 06:00 [entrez]
PHST- 2009/11/26 06:00 [pubmed]
PHST- 2010/01/06 06:00 [medline]
AID - 0008-5472.CAN-09-1622 [pii]
AID - 10.1158/0008-5472.CAN-09-1622 [doi]
PST - ppublish
SO  - Cancer Res. 2009 Dec 15;69(24):9211-8. doi: 10.1158/0008-5472.CAN-09-1622.