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 Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: April 01, 2018
• End date: January 08, 2023
• 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
• 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

(7)

(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; ALVES, RODRIGO NUNES; ESCOBAR, MARIA ISABEL MELO; FERNANDES, CAMILA FELIX DE LIMA; FORTES, AILINE CIBELE DOS SANTOS; SOUZA, MARIA CLARA DA SILVA; BOCCACINO, JACQUELINE MARCIA; CANGIANO, GIOVANNI; SOARES, SAMUEL RIBEIRO; et al. Unconventional Protein Secretion in Brain Tumors Biology: Enlightening the Mechanisms for Tumor Survival and Progression. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, v. 10, p. 17-pg., 2022-06-15. (21/05287-2, 21/13114-0, 18/15557-4, 19/14741-9, 19/11097-1, 20/03714-8, 20/04687-4, 19/12710-9, 17/26158-0, 20/07450-5, 19/06971-4, 20/05443-1, 21/13070-3)

GONCALVES, CONRADO DE C.; PINHEIRO, GLAUCIA M. S.; DAHLSTROM, KATHE M.; SOUTO, DENIO E. P.; KUBOTA, LAURO T.; BARBOSA, LEANDRO R. S.; RAMOS, I, CARLOS H.. On the structure and function of Sorghum bicolor CHIP (carboxyl terminus of Hsc70-interacting protein): A link between chaperone and proteasome systems. Plant Science, v. 296, JUL 2020. (17/26158-0, 18/11948-9, 17/26058-6, 14/00076-0, 16/14228-1, 12/50161-8, 15/15822-1)

PRADO, MARIANA BRANDAO; MELO ESCOBAR, MARIA ISABEL; ALVES, RODRIGO NUNES; COELHO, BARBARA PARANHOS; FERNANDES, CAMILA FELIX DE LIMA; BOCCACINO, JACQUELINE MARCIA; IGLESIA, REBECA PIATNICZKA; LOPES, MARILENE HOHMUTH. Prion Protein at the Leading Edge: Its Role in Cell Motility. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, n. 18, p. 18-pg., 2020-09-01. (19/14952-0, 19/11097-1, 19/14741-9, 17/26158-0, 19/12710-9, 18/15557-4, 20/07450-5, 20/04687-4)

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. (18/15557-4, 17/26158-0, 18/19320-9, 19/12710-9, 19/11097-1, 17/20271-0)

ALVES, RODRIGO NUNES; IGLESIA, REBECA PIATNICZKA; PRADO, MARIANA BRANDAO; MELO ESCOBAR, MARIA ISABEL; BOCCACINO, JACQUELINE MARCIA; FERNANDES, CAMILA FELIX DE LIMA; COELHO, BARBARA PARANHOS; FORTES, AILINE CIBELE; LOPES, MARILENE HOHMUTH. A New Take on Prion Protein Dynamics in Cellular Trafficking. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, n. 20, OCT 2020. (20/07450-5, 17/26158-0, 19/14952-0, 19/11097-1, 20/04687-4, 18/15557-4, 19/12710-9, 19/14741-9)

COELHO, BARBARA PARANHOS; DE LIMA FERNANDES, CAMILA FELIX; BOCCACINO, JACQUELINE MARCIA; DA SILVA SOUZA, MARIA CLARA; MELO-ESCOBAR, MARIA ISABEL; ALVES, RODRIGO NUNES; PRADO, MARIANA BRANDAO; IGLESIA, REBECA PIATNICZKA; CANGIANO, GIOVANNI; MAZZARO, GIULIA LA ROCCA; et al. Multifaceted WNT Signaling at the Crossroads Between Epithelial-Mesenchymal Transition and Autophagy in Glioblastoma. FRONTIERS IN ONCOLOGY, v. 10, NOV 12 2020. (19/14552-1, 19/14952-0, 17/26158-0, 20/04687-4, 19/06971-4, 19/11097-1, 19/12710-9, 20/07450-5, 18/15557-4, 19/14741-9)

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. (18/15557-4, 17/26158-0, 18/19320-9, 19/14952-0, 17/20271-0, 19/12710-9, 19/11097-1)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

PRADO, Mariana Brandão. Prion protein as a stemness regulator in glioblastoma stem cells: its role in the formation and function of multiprotein signaling platforms.. 2023. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.