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System-wide analysis of N-terminal processing and protein diversity in the secretome of tumor cells


The search for biomarkers has been addressed by several investigators in the field of cancer biology, however, given the multitude of etiologic factors associated to oncogenesis, a number of challenges still need to be overcome. The imbalance of cellular homeostasis during oncogenesis has a marked effect on the repertoire of the proteins secreted by malignant cells (cellular secretome), as well as, upon the physiological processing events that occurs during or after protein synthesis. In this regard, the N-termini of eurakyotic proteins as well as the set of post translational modifications (PTMs) at the N-terminus or at the a-amino group has important implications on several ordinary biological processes, such as protein targeting, biological activity and protein turnover. Moreover, proteolytic processing is also responsible for the generation of new protein N-termini and comprises an essentially irreversible cell signaling process, affecting a number of biological pathways. During the last decade or so, investigators have started using high throughput methodologies (so-called 'omics') in order to understand the diversity of cellular secretomes as well as the complexity of PTMs in distinct biological scenarios. In this context, the main goal of this project is to use high resolution mass spectrometry and proteomic analysis to perform a system-wide analysis of protein N-termini derived from secreted proteins in normal and tumoral cultured human cells as well as to correlate the results with the analysis of plasma samples from human patients in order to integrate the analysis with relevant biological pathways that take place during oncogenesis and protein N-terminal processing pathways. (AU)

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Scientific publications (10)
(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)
SALARDANI, MURILO; BARCICK, UILLA; ZELANIS, ANDRE. Assessing proteolytic events in bioinformatic reanalysis of public secretome data from melanoma cell lines. BIOCHEMISTRY AND BIOPHYSICS REPORTS, v. 30, p. 4-pg., . (14/06579-3, 19/07282-8)
LIBERATO, TARCISIO; PESSOTTI, DAYELLE S.; FUKUSHIMA, ISABELLA; KITANO, EDUARDO S.; SERRANO, SOLANGE M. T.; ZELANIS, ANDRE. Signatures of protein expression revealed by secretome analyses of cancer associated fibroblasts and melanoma cell lines. JOURNAL OF PROTEOMICS, v. 174, p. 1-8, . (13/07467-1, 14/06579-3, 17/07897-7)
CAMACHO, MAURICIO FROTA; STUGINSKI, DANIEL R.; ANDRADE-SILVA, DEBORA; NISHIYAMA-JR, MILTON Y.; VALENTE, RICHARD H.; ZELANIS, ANDRE. A snapshot of Bothrops jararaca snake venom gland subcellular proteome. Biochimie, v. 214, p. 10-pg., . (14/06579-3, 19/07282-8)
ZELANIS, ANDRE; SILVA, DEBORA A.; KITANO, EDUARDO S.; LIBERATO, TARCISIO; FUKUSHIMA, ISABELLA; SERRANO, SOLANGE M. T.; TASHIMA, ALEXANDRE K.. A first step towards building spectral libraries as complementary tools for snake venom proteome/peptidome studies. Comparative Biochemistry and Physiology D-Genomics & Proteomics, v. 31, . (13/14651-3, 14/06579-3, 17/20106-9, 13/07467-1, 17/07897-7, 13/13548-4)
PESSOTTI, DAYELLE S.; ANDRADE-SILVA, DEBORA; SERRANO, SOLANGE M. T.; ZELANIS, ANDRE. Heterotypic signaling between dermal fibroblasts and melanoma cells induces phenotypic plasticity and proteome rearrangement in malignant cells. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, v. 1868, n. 12, p. 9-pg., . (14/06579-3, 19/07282-8, 16/16935-7, 13/07467-1)
FRANCISQUINI, RODRIGO; BERTON, RAFAEL; SOARES, SANDRO GOMES; PESSOTTI, DAYELLE S.; CAMACHO, MAURICIO F.; ANDRADE-SILVA, DEBORA; BARCICK, UILLA; SERRANO, SOLANGE M. T.; CHAMMAS, ROGER; NASCIMENTO, MARIA C. V.; et al. Community-based network analyses reveal emerging connectivity patterns of protein-protein interactions in murine melanoma secretome. JOURNAL OF PROTEOMICS, v. 232, . (17/22330-3, 15/21660-4, 13/07375-0, 17/24185-0, 14/06579-3, 19/10817-0, 13/07467-1)
LIBERATO, TARCISIO; FUKUSHIMA, ISABELLA; KITANO, EDUARDO S.; SERRANO, SOLANGE M. T.; CHAMMAS, ROGER; ZELANIS, ANDRE. Proteomic profiling of the proteolytic events in the secretome of the transformed phenotype of melanocyte-derived cells using Terminal Amine Isotopic Labeling of Substrates. JOURNAL OF PROTEOMICS, v. 192, p. 291-298, . (14/06579-3, 13/07467-1, 17/07897-7)
AUGUSTO-DE-OLIVEIRA, CESAR; STUGINSKI, DANIEL R.; KITANO, EDUARDO S.; ANDRADE-SILVA, DEBORA; LIBERATO, TARCISIO; FUKUSHIMA, ISABELLA; SERRANO, SOLANGE M. T.; ZELANIS, ANDRE. Dynamic Rearrangement in Snake Venom Gland Proteome: Insights into Bothrops jararaca Intraspecific Venom Variation. JOURNAL OF PROTEOME RESEARCH, v. 15, n. 10, p. 3752-3762, . (13/07467-1, 14/06579-3)
DIAS, MATHEUS H.; KITANO, EDUARDO S.; ZELANIS, ANDRE; IWAI, LEO K.. Proteomics and drug discovery in cancer. DRUG DISCOVERY TODAY, v. 21, n. 2, p. 264-277, . (12/20186-9, 11/11308-0, 14/06579-3, 13/07467-1)

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