Epigenetic modulations and self-renewal potential of canine mammary cancer cells: the search for potential therapeutic targets

• Grant number: 17/11966-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: November 01, 2017
• End date: December 31, 2020
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Heidge Fukumasu
• Grantee: Pedro Luiz Porfirio Xavier
• Host Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil
• Associated research grant: 14/02493-7 - Mammary tumors of dogs and the cancer stem cell theory: a comparative and translational approach, AP.JP
• Associated scholarship(s): 19/05778-6 - Combined inhibition of BET proteins AND HDACs as an effective strategy for the treatment of mammary cancer: a comparative study, BE.EP.DR

Abstract

Mammary neoplasm as well as other solid tumors may exhibit specifically a cell population hierarchy which determines the development and tumor behavior. Recently, the cancer research has highlighted similarities between a specific cancer cell group and normal stem cells, denominated tumor-initiating cells (TICs). Such similarities as self-renewal potential pointed as a major relevant phenotype affecting intratumoral heterogeneity maintenance and tumor development. Therefore, the discovery and characterization of therapeutic molecules which target TIC self-renewal would be of great relevance to cancer treatment. The aim of this project is to evaluate the effects of epigenetic targets modulation under self-renewal potential of canine mammary cancer cells and to identify possible regulatory regions of self-renewal potential. Based on this purpose, will be evaluated the effects of low and non-cytotoxic doses of 23 specific epigenetic probes in canine mammary cancer cells that exhibit high self-renewal potential determined through of tumorsphere formation assay. Subsequently, the effects of the epigenetic compound which to exhibit the higher inhibitory effect under self-renewal potential will be determined and its effects will be evaluated using molecular approaches. Through global gene expression analysis, regulatory gene pathways associated with self-renewal potential will be identified. Afterward, the effects of the major interest epigenetic compound under the chromatin remodeling of tumorspheres will be evaluated through ATAC-seq technique. Finally, integrating transcriptomic and epigenomic data, we propose to determine regulatory genome regions of self-renewal potential, as well as the characterization of a potential and innovative epigenetic therapy against TICs and cancer. (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)

XAVIER, PEDRO LUIZ PORFIRIO; MUELLER, SUSANNE; FUKUMASU, HEIDGE. Epigenetic Mechanisms in Canine Cancer. FRONTIERS IN ONCOLOGY, v. 10, OCT 23 2020. (19/05778-6, 17/11966-4, 14/02493-7)

XAVIER, PEDRO L. P.; CORDEIRO, YONARA G.; ALEXANDRE, PAMELA A.; PIRES, PEDRO R. L.; SARANHOLI, BRUNO H.; SILVA, EDSON R.; MUELLER, SUSANNE; FUKUMASU, HEIDGE. An epigenetic screening determines BET proteins as targets to suppress self-renewal and tumorigenicity in canine mammary cancer cells. SCIENTIFIC REPORTS, v. 9, NOV 22 2019. (17/11966-4, 19/05778-6, 14/02493-7)

RAQUEL LOZANO GUILHARDUCCI; PEDRO LUIZ PORFIRIO XAVIER; JULIANO COELHO DA SILVEIRA; YONARA DE GOUVEIA CORDEIRO; LUIZ ROBERTO BIONDI; RICARDO DE FRANCISCO STREFEZZI; HEIDGE FUKUMASU. Expressão de LIN28A/B e Let-7 miRNAs em carcinomas mamários caninos. Ciência Rural, v. 52, n. 10, 2022-03-14. (14/02493-7, 17/11966-4, 19/05778-6, 15/10036-8)

Academic Publications

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

XAVIER, Pedro Luiz Porfirio. Exploring epigenetic mechanisms to target mammary cancer cells: a comparative approach. 2020. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Zootecnica e Engenharia de Alimentos (FZE/BT) Pirassununga.