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Role of SOX9-BMI1 in adult neural stem cells and in glioma stem cells

Final Report Summary - SOX-BMI1 (Role of SOX9-BMI1 in adult neural stem cells and in glioma stem cells)

Cancers display remarkable phenotypical and functional intratumoral heterogeneity. The discovery of a rare subpopulation of tumor cells that acquired stem cells properties or originate from stem cell transformation in several malignancies has profound implications for cancer therapy, as these cells are responsible for the origin, progression and recurrence of the tumors.

Glioblastoma multiforme is one of the most aggressive and lethal human malignancies where the cancer stem cells have been identified. However, this research is not translated into significant advances in therapy treatment. The therapeutic protocols present very low success rate and the average survival for patients do not exceed a year and half of life. Factors involved in establishing and maintaining stem cells of normal tissues are activated as part of the tumorigenic process. These stem cell factors are likely to be important for maintaining the characteristics of cancer stem cells. The study of the function of stem cell factors appears to be essential for understanding the biology of glioblastoma and designing effective therapeutic strategies.

SOX9 and BMI1 are essential in multiple processes during embryonic development and regulate the population of stem cells in various tissues including the brain. Both are overexpressed in a wide range of cancers, mainly in tissues where they plays critical roles in stem/progenitor cells. Our group has recently identified that BMI1 is a downstream target of SOX9. The ultimate goal of this translational research project was investigate the clinical relevance of SOX9-BMI1 pathway, characterize its role in the regulation of cancer stem cells and determine whether their overexpression is sufficient to promote cell transformation. To achieve our aims, we have generated a unique set of cellular and animal models to study in vitro and in vivo the biology of adult and cancer stem cells.