Evaluation of transcript levels of PrPc downstream targets and intracellular signaling pathways in glioblastoma stem cells

• Grant number: 20/07450-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2020
• End date: July 31, 2022
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Marilene Hohmuth Lopes
• Grantee: Jacqueline Marcia Boccacino
• 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

Glioblatoma Multifome (GBM) is a highly aggressive and lethal type of tumor derived from glial cells. Its high recurrence rate can be attributed to its resistance to conventional treatments and diffuse growth pattern. Studies show that GBM is maintained by a subpopulation of cells with stem cell like characteristics, denominated Glioblastoma Stem Cells (GSCs). These cells can give rise to highly proliferative cells and invasive cells, contributing to the survival of the tumor. Our group has described the role of the Cellular Prion Protein (PrPC) in the biology of the GSC, being involved in the modulation of proliferation and self-renewal of these cells. PrPC is a GPI-anchored protein, capable of acting as a scaffold protein, forming complexes with multiple proteins, such as stemness markers. Our group has proposed prion protein as a scaffold protein able to modulate the activity of a multiprotein platform on cell membrane involved in stemness, and understanding how this dynamic signaling platform functions in normal neural stem cells and GSCs may help us to better understand brain tumor proliferation and self-renewal. Potential PrPc partners on cell membrane and downstream signaling pathways remain to be characterized and the RNA-seq data might provide potential candidates/intracellular pathways to be explored. Thus, the aim of this study is to validate the potential genes differentially expressed from transcriptome analysis of PrPc-null GSCs and their counterparts. Moreover, data from public databases will be analyzed in order to support our RNA-seq data.

Scientific publications

(5)

(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)

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)

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)