Characterization of enzymes involved in post-translational modifications that modulate protein stability and translocation during the Epithelial-Mesenchymal transition

• Grant number: 17/03960-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2017
• End date: January 31, 2019
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Vitor Marcel Faça
• Grantee: Virgínia Campos Silvestrini
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Cancer is characterized as a set of multifactorial diseases that has in common the disordered growth of cells, which spread to other tissues and organs giving rise to metastases. During the metastasis, several changes comprise protein stability and translocation, including transport of proteins to the membrane, changes in the cytoskeleton, among others. Thus, during the cancer progression and more specifically during metastasis, several points of control are related to protein translocation between cellular sub-compartments. In all the cells, such processes modulation are triggered by signaling cascades dependent on mechanisms finely controlled by post-translational modifications. Recently, some mechanisms have gained more attention because they are based on the translocation and degradation of protein by the ubiquitin-proteasome system. During these processes, target proteins receive post-translational modifications such ubiquitination, sumoylation and neddylation throughout specific enzymes. In this way, they participate of the pathways' fine control in which they are involved. In the present project, it will be evaluated the influence of pathways and mechanisms of ubiquitination/ubiquitin-like, de-ubiquitinases and ubiquitin-proteasome system in the regulation of epithelial-mesenchymal transition (EMT) processes. Breast cancer cell lines will be used as models to EMT induction in response to growth factors simulating the critical stages of metastatic triggering and development. Based on preliminary results obtained in our laboratory during the induction of EMT, enzymes involved in the ubiquitination, sumoylation and nedylation pathways will be selected for modulated through specific chemical inhibitors or interference RNA. Base on this strategy, we will evaluate the role of such enzymes in the control the EMT process. We will also use targeted proteomics methods to quantify and validate the observed molecular alterations. As a result, we expect to identify key-enzymes involved in the processes of ubiquitination, sumoylation or nedylation and that participate in tumor progression. This project will contribute to the research of potential new targets for metastatic cancer therapy. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SILVESTRINI, VIRGINIA CAMPOS; THOME, CAROLINA HASSIBE; ALBUQUERQUE, DANIELE; PALMA, CAMILA DE SOUZA; FERREIRA, GERMANO AGUIAR; LANFREDI, GUILHERME PAUPERIO; MASSON, ANA PAULA; ALBERICI DELSIN, LARA ELIS; FERREIRA, FERNANDA URSOLI; DE SOUZA, FELIPE CANTO; et al. Proteomics analysis reveals the role of ubiquitin specific protease (USP47) in Epithelial to Mesenchymal Transition (EMT) induced by TGF beta 2 in breast cells. JOURNAL OF PROTEOMICS, v. 219, MAY 15 2020. (17/03960-6, 16/03809-3, 13/08135-2)

SILVESTRINI, VIRGINIA CAMPOS; LANFREDI, GUILHERME PAUPERIO; MASSON, ANA PAULA; POERSCH, ALINE; FERREIRA, GERMANO AGUIAR; THOME, CAROLINA HASSIBE; FACA, VITOR MARCEL. A proteomics outlook towards the elucidation of epithelial-mesenchymal transition molecular events. MOLECULAR OMICS, v. 15, n. 5, p. 316-330, OCT 1 2019. (17/03960-6, 16/03809-3, 13/08135-2)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SILVESTRINI, Virgínia Campos. Proteomic analysis of alterations in the ubiquitin-proteasome system during epithelial to mesenchymal transition (EMT). 2019. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.