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Role of the STI1-PrPc interaction in the biology of neural stem cells: physiological and tumoral contexts

Grant number: 07/08410-2
Support type:Regular Research Grants
Duration: October 01, 2008 - March 31, 2011
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Marilene Hohmuth Lopes
Grantee:Marilene Hohmuth Lopes
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Our group has characterized STI1 (stress inducible protein one), a co-chaperone, as a specific cellular prion protein ligand (PrPC), a normal isoform from that protein neurodegenerative disease-related. PrPC-STI1 interaction is able to modulate neuronal survival and differentiation. Futhermore, PrPC plays an important role in the neural stem cell (NSCs) biology and preliminary data from our group show that its interaction with STI1 participates in the auto-renewal of NSCs. NSCs have been involved not only in adult SNC neurogenesis but also in the genesis and control of brain neoplasias particularly gliomas, meduloblastomas and ependimonas. Recent data show that STI1 is secreted either by normal or tumoral astrocytes (glioblastoma cell line) and its interaction with PrPC modulates cellular proliferation of human glioblastoma. Interestingly, recent studies in vivo show that NSCs can be recruited to glioblastoma xenograft being this event associate to decreasing of tumor size and increasing of animal survival. Thus, those data suggest a putative role for STI1 in the brain tumor biology, since the blockage of its interaction with PrPc and its participation in NSCs auto-renewal could modulates the tumor progression. Regarding NSCs as a relevant model to explore gliomas biology and to screening new therapeutic targets, this project has as main goal investigate the PrPc-STI1 participation in the NSCs biology of adult animals and study a possible association of NSCs in brain neoplasias. Finally, the implementation of this project would establish new researcher fields in our laboratory: neurogenesis and study of brain tumor and its association to neurogenesis. (AU)

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)
LOPES, M. H.; SANTOS, T. G.; RODRIGUES, B. R.; QUEIROZ-HAZARBASSANOV, N.; CUNHA, I. W.; WASILEWSKA-SAMPAIO, A. P.; COSTA-SILVA, B.; MARCHI, F. A.; BLEGGI-TORRES, L. F.; SANEMATSU, P. I.; SUZUKI, S. H.; OBA-SHINJO, S. M.; MARIE, S. K. N.; TOULMIN, E.; HILL, A. F.; MARTINS, V. R. Disruption of prion protein-HOP engagement impairs glioblastoma growth and cognitive decline and improves overall survival. Oncogene, v. 34, n. 25, p. 3305-3314, JUN 2015. Web of Science Citations: 12.
SANTOS, TIAGO G.; SILVA, IARA R.; COSTA-SILVA, BRUNO; LEPIQUE, ANA PAULA; MARTINS, VILMA R.; LOPES, MARILENE H. Enhanced Neural Progenitor/Stem Cells Self-Renewal via the Interaction of Stress-Inducible Protein 1 with the Prion Protein. Stem Cells, v. 29, n. 7, p. 1126-1136, JUL 2011. Web of Science Citations: 39.

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