EZH2 is essential for glioblastoma cancer stem cell maintenance.

Details

Serval ID
serval:BIB_1D6675ED54B7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
EZH2 is essential for glioblastoma cancer stem cell maintenance.
Journal
Cancer Research
Author(s)
Suva Mario-Luca, Riggi Nicolo, Janiszewska Michalina, Radovanovic Ivan, Provero Paolo, Stehle Jean-Christophe, Baumer Karine, Le Bitoux Marie-Aude, Marino Denis, Cironi Luisa, Marquez Victor E., Clement Virginie, Stamenkovic Ivan
ISSN
1538-7445[electronic]
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
69
Number
24
Pages
9211-9218
Language
english
Abstract
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.
Keywords
Animals, Cell Line, Tumor, DNA-Binding Proteins/antagonists & inhibitors, DNA-Binding Proteins/biosynthesis, Down-Regulation, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genes, myc, Glioblastoma/genetics, Glioblastoma/metabolism, Humans, Mice, Mice, Inbred NOD, Mice, SCID, Neoplastic Stem Cells/metabolism, Neoplastic Stem Cells/pathology, RNA, Small Interfering/genetics, Transcription Factors/antagonists & inhibitors, Transcription Factors/biosynthesis
Pubmed
Web of science
Open Access
Yes
Create date
13/01/2010 13:12
Last modification date
20/08/2019 12:53
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