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Prion protein as stem regulator in glioblastoma stem cells: its role in the formation and function of multiprotein signaling platforms

Grant number: 17/26158-0
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): April 01, 2018
Effective date (End): August 08, 2021
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal Investigator:Marilene Hohmuth Lopes
Grantee:Mariana Brandão Prado
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):18/19517-7 - The impact of cellular prion protein depletion in the modulation of signaling pathways and expression of prion-like proteins in glioblastoma stem cell biology, BE.EP.DD

Abstract

Glioblastoma Multiforme (GBM) is a tumor formed by glial cells, being the most common and aggressive type of Glioma, with high rates of recurrence and death. Studies show that GBM is maintained by a cell subpopulation with characteristics of stem cells, called Glioblastoma Stem Cells (GSCs). These cells self-renew, promote angiogenesis and invasion, and are chemo and radio-resistant. Thus, GSCs have significant potential as a therapeutic target against glioblastomas. Recent studies show that cellular prion protein (PrPC) emerges as a key factor in the maintenance of GBM and CTGs. PrPC has an important role as scaffold protein, being able to interact with several other proteins of the membrane and the extracellular matrix, forming complexes capable of regulating different functions of the tumor cell. In particular, PrPC is able to interact with Notch (a membrane receptor involved with cell differentiation) by regulating receptor stability and activation of the required signaling pathway in the maintenance of neural stem cells and in the proliferation of tumor cells. Studies indicate that PrPC would be able to recruit locally and activate the EGF receptor, and has also been described as a ligand of L1CAM, a potential molecular marker of CTGs. PrPC co-localizes and is co-expressed with CD44 (a glycoprotein involved in cell-cell interactions) in treatment-resistant breast tumors. In addition, PrPC is also able to modulate cell adhesion proteins such as ±6 integrin, important in the process of tumor invasion. Recent data from our group suggest PrPC as a ligand of CD133 capable of modulating its intracellular traffic in GBM and, consequently, its function. Faced with the ability of PrPC to recruit and interact with proteins implicated in stemness, we propose in this study to evaluate the role of PrPC as a scaffold protein in the modulation of signaling platforms that support the undifferentiated state of GSCs. Therefore the understanding of the biology of GSCs and how these cells interact with their microenvironment through multiprotein complexes of the cell surface is essential for the development of more effective therapies. (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)
IGLESIA, REBECA PIATNICZKA; DE LIMA FERNANDES, CAMILA FELIX; COELHO, BARBARA PARANHOS; PRADO, MARIANA BRANDAO; MELO ESCOBAR, MARIA ISABEL; DONA RODRIGUES ALMEIDA, GUSTAVO HENRIQUE; LOPES, MARILENE HOHMUTH. Heat Shock Proteins in Glioblastoma Biology: Where Do We Stand?. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 20, n. 22 NOV 2019. Web of Science Citations: 0.
DE LIMA FERNANDES, CAMILA FELIX; IGLESIA, REBECA PIATNICZKA; MELO-ESCOBAR, MARIA ISABEL; PRADO, MARIANA BRANDAO; LOPES, MARILENE HOHMUTH. Chaperones and Beyond as Key Players in Pluripotency Maintenance. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, v. 7, AUG 2 2019. Web of Science Citations: 1.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.