RUNX1 and FOXP3 interplay regulates expression of breast cancer related genes
Authors
Recouvreux, Maria SolGrasso, Esteban Nicolas
Echeverria, Pablo Christian
Rocha-Viegas, Luciana
Castilla, Lucio H.
Schere-Levy, Carolina
Tocci, Johanna Melisa
Kordon, Edith Claudia
Rubinstein, Natalia
Document Type
Journal ArticlePublication Date
2016-02-09Keywords
Runx1Foxp3
Rspo3
GJA1
gene expression regulation
Cancer Biology
Cell Biology
Cellular and Molecular Physiology
Molecular Biology
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Show full item recordAbstract
Runx1 participation in epithelial mammary cells is still under review. Emerging data indicates that Runx1 could be relevant for breast tumor promotion. However, to date no studies have specifically evaluated the functional contribution of Runx1 to control gene expression in mammary epithelial tumor cells. It has been described that Runx1 activity is defined by protein context interaction. Interestingly, Foxp3 is a breast tumor suppressor gene. Here we show that endogenous Runx1 and Foxp3 physically interact in normal mammary cells and this interaction blocks Runx1 transcriptional activity. Furthermore we demonstrate that Runx1 is able to bind to R-spondin 3 (RSPO3) and Gap Junction protein Alpha 1 (GJA1) promoters. This binding upregulates Rspo3 oncogene expression and downregulates GJA1 tumor suppressor gene expression in a Foxp3-dependent manner. Moreover, reduced Runx1 transcriptional activity decreases tumor cell migration properties. Collectively, these data provide evidence of a new mechanism for breast tumor gene expression regulation, in which Runx1 and Foxp3 physically interact to control mammary epithelial cell gene expression fate. Our work suggests for the first time that Runx1 could be involved in breast tumor progression depending on Foxp3 availability.Source
Oncotarget. 2016 Feb 9;7(6):6552-65. doi: 10.18632/oncotarget.6771. Link to article on publisher's siteDOI
10.18632/oncotarget.6771Permanent Link to this Item
http://hdl.handle.net/20.500.14038/36686PubMed ID
26735887Related Resources
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Copyright : © 2016 Recouvreux et al.Distribution License
http://creativecommons.org/licenses/by/3.0/ae974a485f413a2113503eed53cd6c53
10.18632/oncotarget.6771
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Except where otherwise noted, this item's license is described as Copyright : © 2016 Recouvreux et al.