Differential PrPC expression and correlated genes in patient-derived Glioblastoma stem cells and its consequence to the tumor maintenance and lineage commitment

• Grant number: 21/13070-3
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: January 01, 2022
• End date: March 31, 2024
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Marilene Hohmuth Lopes
• Grantee: Maria Clara da Silva Souza
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/15557-4 - Prion protein and its partners: emerging targets for glioblastoma stem cell based-therapy, AP.JP2

Abstract

The Glioblastoma Multiforme is a highly aggressive glial tumor, with high recurrence and death rates. Recent studies indicate that the GBM is maintained by a sub-population of cells with stem-cell characteristics, denominated Glioblastoma Stem Cells (GSCs). Recently our group has identified the cellular prion protein as having an important role in the modulation of the GSCs undifferentiated state. PrPC is a GPI-anchored protein capable of interacting with many proteins on the cell surface, creating a signaling platform. The undifferentiated state of the GSCs is modulated by multiple proteins and signaling pathways, including PrPC modulated complexes. When compared to the differentiated GBM, the expression of PrPC increases in GSCs, and this upregulation is an important indicative of the role of the protein in the maintenance of those cells. Also, PrPC loss of function inhibits GSCs self-renewal, proliferation and tumor initiating capabilities. With that in mind, we propose to investigate the molecular mechanisms through which PrPC is able to modulate signaling platforms and the biology of GSCs. (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; 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)

FERNANDES, CAMILA FELIX DE LIMA; COELHO, BARBARA PARANHOS; SOUZA, MARIA CLARA DA SILVA; BOCCACINO, JACQUELINE MARCIA; SOARES, SAMUEL RIBEIRO; DE ARAUJO, JAO PEDRO ALVES; MELO-ESCOBAR, MARIA ISABEL; LOPES, MARILENE HOHMUTH. Extracellular vesicles throughout development: A potential roadmap for emerging glioblastoma therapies. SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, v. 133, p. 10-pg., 2023-01-15. (21/13070-3, 19/14952-0, 19/11097-1, 19/14741-9, 20/05443-1, 18/15557-4, 21/05287-2, 20/07450-5)