Cancers display remarkable phenotypical and functional intratumoral heterogeneity. The discovery of a rare subpopulation of tumor cells that acquired stem cells properties in several malignancies has profound implications for cancer therapy. These cells are suppose to be responsible for the origin, progression and recurrence of the tumors. Thus, new strategies directly targeting cancer stem cells should be important for cancer treatment. Glioblastoma multiforme, the most common and malignant brain primary cancer, present very low success rate in the actual therapeutic protocols and the average survival for patients do not exceed a year of life. This can be partially explained because they contain a population of glioma stem cells.
Factors involved in establishing and maintaining stem cells of normal tissues are activated as part of the tumorigenic process. It is likely that these stem cell factors are important for providing and maintaining the characteristics of cancer stem cells. SOX9 and BMI1 are transcriptor factors essential in multiple processes during embryonic development and in the regulation of stem cells in various tissues including the brain. Both are often overexpressed in cancer, mainly in tissues where they plays critical roles in stem/progenitor cells. Our group has recently identified that BMI1 is a direct downstream target of SOX9. The goals of this translational research project is investigate the clinical relevance of SOX9-BMI1 in glioblastoma, characterize its role in the regulation of glioma stem cells and determine whether Sox9-Bmi1 concomitant overexpression is sufficient to induce neural stem cell transformation and cause gliomas. To achieve our aims, we will generate a unique set of cellular and animal models to study in vitro and in vivo the biology of neural and glioma stem cells
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