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GSE15757
Homo sapiens
9 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
We found the PRC2 component EZH2 to be upregulated by the pathognomonic fusion oncogene EWS-FLI1 in Ewing tumors and mesenchymal stem cells (Richter GH et al., Proc Natl Acad Sci U S A. 2009;106:5324-9). Downregulation of EZH2 by RNA interference in Ewing tumor cell lines suppressed oncogenic transformation in vitro and in vivo. These data suggest that EZH2 might play a central role in Ewing Tumor pathology.
Publication Title
Epigenetic maintenance of stemness and malignancy in peripheral neuroectodermal tumors by EZH2.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This study aimed to explore the role of the Zyxin-related protein TRIP6 (thyroid receptor interacting protein 6) in Ewing's sarcoma (ES). By interrogation of published miccroarray data, we observed that of all seven Zyxin-proteins only TRIP6 is highly overexpressed in ES compared to normal tissues. RNA interference experiments and subsequent microarray and gene-set enrichment analyses indicated that TRIP6 expression is associated wth a pro-proliferative and pro-invasive transcriptional signature. Consistently, functional assays demonstrated that TRIP6 promotes migration, invasion, long-term proliferation and clonogencity of ES cells.
Publication Title
The Zyxin-related protein thyroid receptor interacting protein 6 (TRIP6) is overexpressed in Ewing's sarcoma and promotes migration, invasion and cell growth.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Ewing Tumors (ET) are highly malignant tumors, localized in bone or soft tissue and are molecularly defined by ews/ets translocations. We identified histone methyl-transferase Enhancer of Zeste, Drosophila, Homolog 2 (EZH2) to be increased in ET. EZH2s suppressive activity maintains stemness in normal and malignant cells. Here we found EZH2 to be upregulated by the pathognomonic fusion oncogene EWS-FLI1 in ET and mesenchymal stem cells. Downregulation of EZH2 by RNA interference in ET suppressed oncogenic transformation by inhibiting clonogenicity in vitro. Similarly, tumor development and metastasis in immunodeficient Rag2-/-C-/- mice was suppressed. EZH2-mediated gene silencing was shown to be dependent on histone deacetylase (HDAC) activity. Subsequent microarray analysis of EZH2 knock down, HDAC-inhibitor treatment and confirmation in independent assays revealed an undifferentiated phenotype maintained by EZH2 in ET. Downregulation of EZH2 decreased histone H3 lysine 27 trimethylation (H3K27me3) at target loci. EZH2 regulated stemness genes such as nerve growth factor receptor (NGFR) as well as genes involved in neuroectodermal differentiation (EMP1, EPHB2, GFAP, GAP43). These data suggest that EZH2 might play a central role in Ewing Tumor pathology shaping the oncogenicity and stem cell phenotype of this tumor presumably by epigenetic regulation.
Publication Title
EZH2 is a mediator of EWS/FLI1 driven tumor growth and metastasis blocking endothelial and neuro-ectodermal differentiation.
Sample Metadata Fields
No sample metadata fields
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