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Year of publication
Has Fulltext
- yes (82)
Is part of the Bibliography
- no (82)
Keywords
- LHC (7)
- ALICE (3)
- ALICE experiment (3)
- Hadron-Hadron Scattering (3)
- pp collisions (3)
- Beauty production (2)
- Single electrons (2)
- 900 GeV (1)
- Breast cancer (1)
- CVID (1)
Institute
Xavier, Pedro L. P. ; Cordeiro, Yonara G. ; Alexandre, Pâmela A. ; Pires, Pedro R. L. ; Saranholi, Bruno H. ; Silva, Edson R. ; Müller, Susanne ; Fukumasu, Heidge
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.