Molecular and functional characterization of eEF2K in pediatric medulloblastoma

• Grant number: 21/10669-1
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: January 01, 2024
• Status: Discontinued
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Carlos Alberto Scrideli
• Grantee: Jessica Oliveira de Santis
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 24/06469-5 - Effect of eEF2K on energy sources metabolism in Group 3 Medulloblastoma cells, BE.EP.DR

Abstract

Medulloblastoma (MB) is the most common pediatric malignant tumor of the central nervous system (CNS), representing approximately 20% of CNS tumors in children and adolescents. For these patients, the five-year overall survival (OS) is 40 to 90%, with variations between the molecular subgroups of MB (SHH, WNT, Group 3 and 4), among which Group 3 and SHH with TP53-mutated represent the most aggressive subgroups and those with the worst prognosis. Increased energy metabolism is one of the cellular processes associated with increased malignancy in these tumors, and regulation of metabolism is essential for tumor cell survival. One of the proteins that stimulate metabolic reprogramming is eEF2K, a kinase that inhibits its substrate eEF2, a protein that plays a role in protein translation. Under stressful environments, such as nutrient deprivation and hypoxia, eEF2K is activated to decrease energy consumption during translation, allowing the cell to survive in unfavorable conditions. Recently, metabolic reprogramming has been suggested as a promising therapeutic target for different tumors, including MB. Based on the literature, there are only a few recent reports detailing the role of eEF2K in MB and its impact on tumor development. Thus, this project aims to evaluate the functional and molecular effects of eEF2K modulation, as well as the cellular metabolism of high-risk tumors to assess its potential use in combination therapy in pediatric MB.