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

Grant number: 17/11966-4
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): November 01, 2017
Effective date (End): December 31, 2020
Field of knowledge:Agronomical Sciences - Veterinary Medicine - Animal Pathology
Principal Investigator:Heidge Fukumasu
Grantee:Pedro Luiz Porfirio Xavier
Home 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 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. Web of Science Citations: 0.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.