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

• Grant number: 14/06579-3
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: March 01, 2015
• End date: February 28, 2019
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: André Zelanis Palitot Pereira
• Grantee: André Zelanis Palitot Pereira
• Host Institution: Instituto de Ciência e Tecnologia (ICT). Universidade Federal de São Paulo (UNIFESP). Campus São José dos Campos. São José dos Campos , SP, Brazil
• Associated scholarship(s): 17/07897-7 - Proteolytic processing analysis in the secretome of melanoma tumor cells, BP.IC; 17/01374-2 - Prospection of melanoma markers associated with protein N-terminal processing in human plasma samples, BP.MS

Abstract

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)

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)

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, OCT 2016. (13/07467-1, 14/06579-3)

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, FEB 10 2019. (14/06579-3, 13/07467-1, 17/07897-7)

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, FEB 2016. (12/20186-9, 11/11308-0, 14/06579-3, 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, FEB 10 2021. (17/22330-3, 15/21660-4, 13/07375-0, 17/24185-0, 14/06579-3, 19/10817-0, 13/07467-1)

DE MORAIS, JULIANA A.; ZELANIS, ANDRE. Bioinformatic reanalysis of public proteomics data reveals that nuclear proteins are recurrent in cancer secretomes. TRAFFIC, v. 23, n. 2, DEC 2021. (19/07282-8, 14/06579-3)

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., 2022-07-01. (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, SEP 2019. (13/14651-3, 14/06579-3, 17/20106-9, 13/07467-1, 17/07897-7, 13/13548-4)

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, MAR 1 2018. (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., 2023-06-17. (14/06579-3, 19/07282-8)

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., 2020-12-01. (14/06579-3, 19/07282-8, 16/16935-7, 13/07467-1)