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Uncovering the role of CRTC1-MAML2 translocation in salivary Mucoepidermoid Carcinoma: a clinicopathological, molecular and proteomic study

Grant number: 19/26676-7
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): September 01, 2020
Effective date (End): February 29, 2024
Field of knowledge:Health Sciences - Dentistry
Principal researcher:Pablo Agustin Vargas
Grantee:Maria Eduarda Pérez de Oliveira
Home Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil
Associated scholarship(s):21/10810-6 - Proximity-Dependent Biotinylation for the identification of interacting proteins in salivary gland cells harbouring the CRTC1-MAML2 translocation, BE.EP.DR

Abstract

Mucoepidermoid Carcinoma (MEC) is the most common malignant salivary gland tumor. The CRTC1-MAML2 translocation has been identified in about 50% of cases and is considered to be associated with better survival rates, although some authors have questioned its prognostic value. The mechanism of action of CRTC1-MAML2 translocation is complex and may influence several important pathways in tumorigeneses. Therefore, it is important to better understand how the translocation and its products affect the development of MEC to then develop efficient target therapies. The objectives of this innovative and multidisciplinary study are (1) to identify the prognostic value of CRTC1-MAML2 in a representative sample of MEC; (2) understand if the translocation influences the proteomic profile of CME; and (3) understand how key proteins identified as deregulated in patient samples influence tumour development in an in vitro model. We will initially investigate the presence of CRTC1-MAML2 and compare the survival time of Translocation-Positive (TP) and Translocation-Negative (TN) MEC patients. The proteomic profile of TP and TN cases will be determined by mass spectrometry. After bioinformatics analysis, promising protein targets that appear to be involved in tumour development and progression will be selected. We will evaluate the role of these proteins in regulating cell survival, invasion and migration and activation of signalling pathways in primary salivary gland cells in which the translocation was induced by stable transfection of the CRTC1-MAML2 vector. Thus, this research project will significantly contribute to a better understanding of the role of CRTC1-MAML2 translocation in MEC development and progression. It might contribute with new diagnosis, prognosis and therapeutical approaches. (AU)

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