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Effect of the O-GlcNacylation pathway on osteosarcoma invasion and migration

Grant number: 23/03640-2
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Start date: May 01, 2023
End date: April 30, 2024
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal Investigator:Sandra Yasuyo Fukada Alves
Grantee:Nádia Yuri Yonamine
Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:19/08568-2 - Investigation of the extracellular vesicles (VEs) role in the initiation, propagation, regeneration, and modeling of biological mineralization, AP.TEM

Abstract

Osteosarcoma is a primary bone tumor that can affect children and adolescents, and has an invasive profile with high rates of metastasis. The main therapeutic approach for osteosarcoma is surgical resection which, when metastatic, has a 5-year survival of less than 30%. O-GlcNacylation is a post-translational modification that consists of the incorporation of O-GlcNac (O-linked-²-N-acetylglucosamine) into serine and threonine residues of intracellular, cytoplasmic and nuclear proteins. Therefore, O-GlcNacylation of proteins has been associated with several diseases, including diabetes, neurodegenerative diseases and several types of cancer. The O-GlcNacylation pathway has been extensively studied in the tumor context as it can activate important signaling pathways in tumorigenesis. In some tumors, the activation of several proteins that participate in the processes of epithelial-mesenchymal transition, migration and cell invasion has been associated with the O-GlcNacylation pathway. However, in osteosarcoma, the study of this pathway is limited to the analysis of the gene expression of its components associated with clinical data from patients. Thus, this project aims to evaluate the function of the O-GlcNacylation pathway in osteosarcoma cell lines, mainly in the processes of epithelial-mesenchymal transition, migration and cell invasion.

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