The role of disulfide isomerase proteins on the acquisition of chemoresistance by temozolomide-treated glioblastoma cells

• Grant number: 21/02029-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2021
• End date: July 31, 2022
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Fabiana Henriques Machado de Melo
• Grantee: Rafael Garcia Pinetti
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Glioblastoma is the primary tumor of the central nervous system (CNS) with the highest incidence and worst prognosis. Despite advances in molecular analysis and imaging of neoplastic tissues, glioblastoma remains without a therapeutic option with the prospect of complete tumor remission. Its genetic profile is variable both between patients and between different moments of tumor progression, making it very difficult to develop effective target-therapies. In this context, one of the metabolic functions that has been widely explored for the treatment of glioblastoma, as well as other refractory tumors, and that shows potential involvement in the chemoresistance of tumor cells, is that of the dithiol/disulfide oxidoreductase activity of the disulfide isomerase proteins. The list of functions described for this protein family has been expanding at an ever-growing pace in recent years, diverging from its initially described chaperone activity to be implicated in stress signaling and cell apoptosis pathways, and in the acquisition of tumor malignancy characteristics. Thus, the objective of this project is to evaluate the modulation performed by PDIA6 on the endoplasmic reticulum stress response mechanism called (unfolded protein response - UPR), compared to the role of the PDIA5 isoform, which has a known interaction with reticular stress sensors. (AU)