Beschreibung:
<jats:title>Abstract</jats:title>
<jats:p>Glioblastoma multiforme (GBM), the most aggressive primary brain tumor, displays an enrichment gene expression related to a stem cell signature. Sox2, a major stemness factor involved in pluripotency and in the maintenance of neural stem cell identity, has been described as frequently overexpressed in poorly differentiated gliomas. However, the role that this molecule plays in brain tumors remains under investigation. In this study, we sought to ascertain the Sox2 potential function in the control of self-renewal of brain tumor stem cells (BTSCs) and the malignant phenotype of gliomas. Our results showed Sox2 expression in human surgical malignant gliomas. In addition, Sox2 expression was significantly higher in the BTSC lines than in established glioma cell lines. Downmodulation of Sox2 in BTSCs by using siRNA resulted in the loss of the self-renewal properties of this cell population, and modification in the pattern of expression of markers related with stem cells properties and differentiation. These results are of major importance since, in the TCGA, we observed Sox2 overexpression in more than 80% of the samples (n=188), gene amplification of SOX2 in 18% of the individuals, and hypomethylation of the promoter in about 90% of the samples when compared with normal tissue, suggesting the relevance of this transcription factor in the malignant phenotype of GBMs. In this regard, our results demonstrated that SOX2 plays a prominent role in the invasive and migratory capabilities of both BTSCs and established glioma cell lines. Thus, ectopic expression of Sox2 was sufficient to induce invasion of glioma cells and knockdown experiments demonstrated that Sox2 is essential for maintaining the invasive properties of glioma cells. Therefore, these results identify a multi-functional aspect of Sox2 as both, a stemness promoting molecule and an essential pro-invasive protein, elucidating the possibility of targeting Sox2 for glioma therapy.</jats:p>
<jats:p>Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3307. doi:10.1158/1538-7445.AM2011-3307</jats:p>