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SOX9 regulates glioblastoma stem cell activity

Paula Aldaz, IIS Biodonostia Pº Doctor Begiristain s/n 20014 San Sebastián (Gipuzkoa) ; Idoia Garcia, Sergio Torres, Jorge Villanua, Irune Ruiz, Nicolás Samprón; Ander Matheu IIS Biodonostia

Glioblastoma multiforme (GBM) is the most frequent and lethal primary brain tumor, which exhibits an extremely poor prognosis characterized by an average survival of 15 months. GBM contains a subpopulation of glioma stem cells (GSC) with self-renewal potential that are crucial drivers of tumor initiation, recurrence and resistance to therapies. Therefore, it is critical to identify the molecular mechanisms responsible to maintain this ability in order to develop novel therapeutic targets and strategies.

In an effort to define these factors, we have identified that SOX9, a transcription factor whose activity is associated with the maintenance of stem cell activity in different tissues including the brain, plays an important oncogenic role in glioblastoma. Thus, levels of SOX9 are enriched in the subpopulation of GSCs. Moreover, SOX9 knockdown induces glioma stem cells differentiation and senescence whilst SOX9 overexpression increases self-renewal potential, tumor initiation potential and therapy resistance. Moreover, SOX9 expression is elevated in biopsies from a subset of patients with poor prognosis postulating that SOX9 inhibition is a promising strategy to combat chemotherapy resistance.

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