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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

An epigenetic screening determines BET proteins as targets to suppress self-renewal and tumorigenicity in canine mammary cancer cells

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Xavier, Pedro L. P. [1] ; Cordeiro, Yonara G. [1] ; Alexandre, Pamela A. [1, 2] ; Pires, Pedro R. L. [1] ; Saranholi, Bruno H. [3] ; Silva, Edson R. [4] ; Mueller, Susanne [5] ; Fukumasu, Heidge [1]
Total Authors: 8
[1] Univ Sao Paulo, Fac Anim Sci & Food Engn, Dept Vet Med, Lab Comparat & Translat Oncol LOCT, Pirassununga - Brazil
[2] CSIRO Agr & Food, Commonwealth Sci & Ind Res Org, Brisbane, Qld - Australia
[3] Univ Fed Sao Carlos, Dept Genet & Evolut, Sao Carlos, SP - Brazil
[4] Univ Sao Paulo, Fac Anim Sci & Food Engn, Dept Vet Med, Pirassununga - Brazil
[5] Goethe Univ Frankfurt, Buchmann Inst Mol Life Sci, Struct Genom Consortium, Frankfurt - Germany
Total Affiliations: 5
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 9, NOV 22 2019.
Web of Science Citations: 0

Targeting self-renewal and tumorigenicity has been proposed as a potential strategy against cancer stem cells (CSCs). Epigenetic proteins are key modulators of gene expression and cancer development contributing to regulation and maintenance of self-renewal and tumorigenicity. Here, we have screened a small-molecule epigenetic inhibitor library using 3D in vitro models in order to determine potential epigenetic targets associated with self-renewal and tumorigenicity in Canine Mammary Cancer (CMC) cells. We identified inhibition of BET proteins as a promising strategy to inhibit CMC colonies and tumorspheres formation. Low doses of (+)-JQ1 were able to downregulate important genes associated to self-renewal pathways such as WNT, NOTCH, Hedgehog, PI3K/AKT/mTOR, EGF receptor and FGF receptor in CMC tumorspheres. In addition, we observed downregulation of ZEB2, a transcription factor important for the maintenance of self-renewal in canine mammary cancer cells. Furthermore, low doses of (+)-JQ1 were not cytotoxic in CMC cells cultured in 2D in vitro models but induced G2/M cell cycle arrest accompanied by upregulation of G2/M checkpoint-associated genes including BTG2 and CCNG2. Our work indicates the BET inhibition as a new strategy for canine mammary cancers by modulating the self-renewal phenotype in tumorigenic cells such as CSCs. (AU)

FAPESP's process: 17/11966-4 - Epigenetic modulations and self-renewal potential of canine mammary cancer cells: the search for potential therapeutic targets
Grantee:Pedro Luiz Porfirio Xavier
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 19/05778-6 - Combined inhibition of BET proteins AND HDACs as an effective strategy for the treatment of mammary cancer: a comparative study
Grantee:Pedro Luiz Porfirio Xavier
Support type: Scholarships abroad - Research Internship - Doctorate
FAPESP's process: 14/02493-7 - Mammary tumors of dogs and the cancer stem cell theory: a comparative and translational approach
Grantee:Heidge Fukumasu
Support type: Research Grants - Young Investigators Grants