SET and sphingolipids in head and neck squamous cell carcinoma: signaling, targets and antiumoral therapy

• Grant number: 16/19103-2
• Support type: Research Projects - Thematic Grants
• Duration: July 01, 2018 - June 30, 2023
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Andréia Machado Leopoldino
• Grantee: Andréia Machado Leopoldino
• Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Assoc. researchers: Carlos Curti ; Luciana Oliveira de Almeida ; Luiz Carlos Conti de Freitas ; Norberto Peporine Lopes
• Associated scholarship(s): 19/22663-8 - Candidate biomarkers selection of human oral cancer by mass spectrometry coupled to high-performance liquid chromatography, BP.PD; 20/00101-5 - Different experimental strategies and approaches for the study of molecular markers in cancer, BP.TT; 18/17480-9 - Study of SET and sphingolipids in head and neck cancer: signaling, targets and antitumor therapy, BP.PD; 18/14225-8 - Study of sphingosine kinase 2 and set proteins in sphingolipids signaling in Head and Neck Cancer, BP.DD

Abstract

Despite the reached breakthrough in the treatment of some cancer types, the search for new therapeutic targets and antitumor therapy strategies to overcome tumor metastases, relapse, and resistance to therapy, is required. The present research proposal aims to identify evidences on the role of SET protein regarding sphingolipid signaling pathway, as well as the sphingolipids role, in head and neck squamous cell carcinoma (HNSCC). This approach can identify new therapeutic targets that may lead to new anticancer treatments. Several experimental approaches will be employed either in vitro or in vivo. We will perform studies in human cell lines, tumor samples, and serum of patients with cancer. In addition, different methods will be used to achieve the proposed goals, such as (i) sphingolipid analysis by mass spectrometry, (ii) post translational modifications of proteins by Western blotting, (iii) cell distribution of proteins by immunohistochemistry, immunofluorescence or Western blotting (subcellular fractionation), (iv) RNA and miRNAs quantification by real-time PCR, (v) DNA sequencing, (vi) RNA interference using either siRNA or shRNA, (vii) ectopic expression using vectors containing cDNAs of interest, (viii) flow cytometry for cell cycle analysis and characterization of cell types using antibodies, (ix) angiogenesis using HUVEC cells, and (x) cell viability, invasion and clonogenic assays. These studies, in addition to the tumor formation in nude mice using the xenograft model of human tumor cell lines and murine carcinoma cell lines in syngeneic mouse model, can both improve the knowledge on sphingolipid signaling in head and neck cancer and led to new mechanistic/therapeutic approaches for cancer. (AU)

Scientific publications

(4)

(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)

GOTO, RENATA NISHIDA; SOBRAL, LAYS MARTIN; STRINGHETTA-PADOVANI, KARINA; GARCIA, CRISTIANA B.; DA SILVA, GABRIEL; VITEK, MICHAEL P.; LEOPOLDINO, ANDREIA MACHADO. Synergic effect of OP449 and FTY720 on oral squamous cell carcinoma. European Journal of Pharmacology, v. 882, SEP 5 2020. Web of Science Citations: 0.

FUGIO, LAIS BRIGLIADORI; COELI-LACCHINI, FERNANDA B.; LEOPOLDINO, ANDREIA MACHADO. Sphingolipids and Mitochondrial Dynamic. CELLS, v. 9, n. 3 MAR 2020. Web of Science Citations: 0.

SOUSA, LUCAS OLIVEIRA; SOBRAL, LAYS MARTIN; DE ALMEIDA, LUCIANA OLIVEIRA; GARCIA, CRISTIANA BERNADELLI; GREENE, LEWIS JOEL; LEOPOLDINO, ANDREIA MACHADO. SET protein modulates H4 histone methylation status and regulates miR-137 level in oral squamous cell carcinoma. Epigenomics, v. 12, n. 6, p. 475-485, MAR 2020. Web of Science Citations: 0.

OUCHIDA, AMANDA TOMIE; UYEMURA, VALERIA TUDELLA; QUEIROZ, ANDRE LIMA; BRAUER, VERONICA SOARES; CAVALCANTI-NETO, MARINALDO PACIFICO; SOUSA, LUCAS OLIVEIRA; UYEMURA, SERGIO AKIRA; CURTI, CARLOS; LEOPOLDINO, ANDREIA MACHADO. SET protein accumulation prevents cell death in head and neck squamous cell carcinoma through regulation of redox state and autophagy. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, v. 1866, n. 4, p. 623-637, APR 2019. Web of Science Citations: 1.