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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 30, 2009 |
| Title |
DZNep-treated glioblastoma multiforme cancer stem cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Overexpression of the Polycomb group protein Enhancer of Zeste Homolog 2 (EZH2) occurs in diverse malignancies, including prostate cancer, breast cancer, and glioblastoma multiforme (GBM) (1). 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 down-regulation by shRNA, strongly impairs GBM cancer stem cell self-renewal in vitro and tumor-initiating capacity in vivo. Using genome-wide expression analysis of DZNep-treated GBM cancer stem cells, we found the expression of c-myc, recently reported to be essential for GBM cancer stem cells, to be strongly repressed upon EZH2 depletion. Specific shRNA-mediated down-regulation of EZH2 in combination with chromatin immunoprecipitation (ChIP) experiments revealed that c-myc is a direct target of EZH2 in GBM cancer stem cells. Taken together, our observations provide evidence that direct transcriptional regulation of c-myc by EZH2 may constitute a novel mechanism underlying GBM cancer stem cell maintenance and suggest that EZH2 may be a valuable new therapeutic target for GBM management.
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| Overall design |
Three samples of cancer stem-cell enriched gliospheres from primary glioblastoma multiforme cell cultures were treated with DZNep. Untreated gliospheres from the same cultures were used as controls.
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| Contributor(s) |
Suvà M, Riggi N, Janiszewska M, Radovanovic I, Provero P, Stehle J, Baumer K, Le Bitoux M, Marino D, Cironi L, Marquez VE, Clément V, Stamenkovic I |
| Citation(s) |
19934320 |
| Submission date |
Sep 17, 2009 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Paolo Provero |
| E-mail(s) |
paolo.provero@unito.it
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| Organization name |
University of Turin
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| Department |
Molecular Biotechnology and Health Sciences
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| Street address |
Via Nizza 52
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| City |
Torino |
| ZIP/Postal code |
I-10100 |
| Country |
Italy |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA119483 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE18150_RAW.tar |
35.4 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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