Study of the MAPK/ERK pathway in the proliferation of glioblastoma stem cells induced by the PrPc-STI1 complex

• Grant number: 15/04122-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2015
• End date: April 30, 2016
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Marilene Hohmuth Lopes
• Grantee: Mariana Brandão Prado
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

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 Interestingly, unpublished data from our group have showed that the interaction between PrPC and STI1 is able to promote self-renewal and proliferation of GSCs, suggesting the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.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

IGLESIA, REBECA PIATNICZKA; PRADO, MARIANA BRANDAO; CRUZ, LILIAN; MARTINS, VILMA REGINA; SANTOS, TIAGO GOSS; LOPES, MARILENE HOHMUTH. Engagement of cellular prion protein with the co-chaperone Hsp70/90 organizing protein regulates the proliferation of glioblastoma stem-like cells. STEM CELL RESEARCH & THERAPY, v. 8, APR 17 2017. (13/19860-0, 15/04122-9, 11/13906-2, 09/14027-2)