Glioblastoma multiforme (GBM) is a tumor derived from glial cells, and is considered one of the most agressive type, with a high rate of recurrence and death. Currently, there is no effective treatment for this disease and its spread pattern prevents the complete removal by surgery. Studies show that the GBM is maintained by a subpopulation of cells with stem cell characteristics, the glioblastoma stem cells (GSCs). These cell are phenotypically similar to normal neural stem cells and have the potential capacity to self-renewal. GSCs are chemo and radio resistent and are also able to remain in a quiescent state, which would explain the tumor high recurrence rate.Our group has demonstrated a central role of cellular prion protein (PrPC) and its main ligand, the co-chaperone stress inducible protein one or heat-shock organizing protein (STI1/HOP) in the control of growth glioblatoma in vitro and in vivo. The inhibition of PrP-STI1 complex by a specific peptide is able to delay tumor growth and significantly increases animal survival in xenograft models in immunodeficient mice. Additionaly, in vitro assays shows that the signaling pathway ERK1/2 is required for glioblastoma cell proliferation in PrP-STI1 complex dependent-manner. Interestingly, unpublished data from our group have showed that the interaction between PrPC and STI1 is able to promote self-renewal and proliferation of GSCs, suggesting the participation of the complex in the formation and maintenance of GBM.Given these data, this study aim to evaluate the participation of the ERK1/2 pathway in GSCs proliferation mediated by the PrPC-STI1 complex. Thus, it is expected that a better understanding of the mechanisms involved in the maintenance of GBM may assist in the development of new therapies and identification of target molecules.
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