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Targeted proteomics of subcellular translocation during epithelial to mesenchymal transition (EMT)


The proteome is a multidimensional and highly dynamic system, in which proteins have interconnected properties that characterizes the phenotype of a cell or organism. The accurate measurement of such properties is vey challenging because of protein dynamics and diversity. Recent advances in proteomics mass spectrometry have driven integrated measurements of protein abundance, cellular localization, turnover, posttranslational modifications (PTMs), etc., allowing a better understanding of complex physiological processes. Determination of protein cellular localization and traffic is an important step towards understanding protein function in health and disease. Indeed, it is well documented that aberrant protein localization is directly involved in pathogenesis such as cancer. The aberrant cellular localization can be frequently associated to protein PTMs or uncommon protein-protein interactions. Therefore, multidimensional proteomics becomes an attractive strategy to aid the understanding of complex mechanisms in disease. With this objective, we plan to evaluate quantitatively protein cellular localization changes, as well as the possible PTMs involved, associated to models of cancer metastasis. For that, we will take the benefits of epithelial to mesenchymal transition (EMT) models developed in our laboratory to represent cancer progression and metastasis. The multidimensional changes in the proteome will be analyzed with a combined strategy of subcellular fractionation and targeted proteomics, which allows the generation of protein correlation profiles (PCP) that represent a temporal and quantitative evaluation of subcellular changes during EMT. The functional inhibition and knockdown/knockout of protein targets will contribute to validate the role of protein translocation in the EMT process. Altogether, we foresee the contribution of this project in the field of multidimensional proteomics method development and also to uncover and verify important cellular processes that occur during EMT and that can represent new options of potential therapeutic targets for metastatic cancer. (AU)

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Scientific publications (6)
(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)
POERSCH, ALINE; GRASSI, MARIANA L.; PALMA, CAMILA S.; CARVALHO, VINICIUS P.; LANFREDI, GUILHERME P.; CARRARA, HELIO H. A.; CANDIDO DOS REIS, FRANCISCO J.; FACA, VITOR M.. Profile of ovarian cancer tumor fluid using high-throughput and targeted proteomic analysis. MOLECULAR CANCER THERAPEUTICS, v. 17, n. 1, p. 2-pg., . (13/08135-2, 16/03809-3)
PALMA, CAMILA S.; GRASSI, MARIANA L.; THOME, CAROLINA H.; POERSCH, ALINE; LANFREDI, GUILHERME P.; FACA, VITOR M.. Proteomic analysis of epithelial-to-mesenchymal transition induced by EGF in breast cancer cells. MOLECULAR CANCER THERAPEUTICS, v. 17, n. 1, p. 2-pg., . (15/08693-0, 16/03809-3, 13/08135-2)
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, . (17/03960-6, 16/03809-3, 13/08135-2)
LANFREDI, GUILHERME P.; THOME, CAROLINA H.; FERREIRA, GERMANO A.; SILVESTRINI, VIRGINIA C.; MASSON, ANA P.; VARGAS, ALESSANDRA P.; GRASSI, MARIANA L.; POERSCH, ALINE; CANDIDO DOS REIS, FRANCISCO J.; FACA, VITOR M.. Analysis of ovarian cancer cell secretome during epithelial to mesenchymal transition reveals a protein signature associated with advanced stages of ovarian tumors. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, v. 1869, n. 6, . (13/07675-3, 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, . (17/03960-6, 16/03809-3, 13/08135-2)
THOME, CAROLINA HASSIBE; FERREIRA, GERMANO AGUIAR; PEREIRA-MARTINS, DIEGO ANTONIO; DOS SANTOS, GUILHERME AUGUSTO; ORTIZ, CESAR ALEXANDER; BOTELHO DE SOUZA, LUCAS EDUARDO; SOBRAL, LAYS MARTINS; ARAUJO SILVA, CLEIDE LUCIA; SCHEUCHER, PRISCILA SANTOS; GIL, CRISTIANE DAMAS; et al. NTAL is associated with treatment outcome, cell proliferation and differentiation in acute promyelocytic leukemia. SCIENTIFIC REPORTS, v. 10, n. 1, . (13/07675-3, 13/08135-2, 16/03809-3, 17/23117-1)

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