| Full text | |
| Author(s): |
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
|
| Affiliation: | [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 |
| Abstract | |
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 Opportunities: | 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 Opportunities: | 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 Opportunities: | Research Grants - Young Investigators Grants |