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Proximity-Dependent Biotinylation for the identification of interacting proteins in salivary gland cells harbouring the CRTC1-MAML2 translocation

Grant number: 21/10810-6
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): June 15, 2022
Effective date (End): June 14, 2023
Field of knowledge:Health Sciences - Dentistry
Principal researcher:Pablo Agustin Vargas
Grantee:Maria Eduarda Pérez de Oliveira
Supervisor abroad: Lynne Bingle
Home Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil
Research place: University of Sheffield, England  
Associated to the scholarship:19/26676-7 - Uncovering the role of CRTC1-MAML2 translocation in salivary Mucoepidermoid Carcinoma: a clinicopathological, molecular and proteomic study, BP.DR

Abstract

Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumour. The CRTC1-MAML2 translocation has been identified in approximately 50% of cases and is associated with improved survival rates, although some authors have questioned its prognostic value. The mechanism of action of the CRTC1-MAML2 translocation is complex and may influence several important pathways in tumorigenesis. Therefore, a better understanding as to how the translocation and its products affect the development of MEC is important when considering the development of efficient target therapies. The aims of this study are (1) investigate the impact of the CRTC1-MAML2 translocation in salivary MEC by screening for physiologically relevant protein-protein interactions using proximity-dependent biotin identification (BioID) and (2) understand how key proteins identified as being deregulated influence tumour development in an in vitro model. Novel protein-protein interactions will be determined using the BioID method and resulting biotinylated proteins identified by mass spectrometry. Bioinformatics analysis will allow promising targets involved in tumour development and progression to be selected and evaluation of their role in regulating cell survival, invasion and migration and activation of signalling pathways in primary salivary gland cells in which the translocation has been induced by stable transfection of the CRTC1-MAML2 vector. This research project will significantly contribute to a better understanding of the role of CRTC1-MAML2 translocation in MEC development and progression and identify novel diagnostic, prognostic and therapeutical targets.

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