UMMS Affiliation

Department of Molecular, Cell and Cancer Biology; UMass Metabolic Network

Date

2-9-2016

Document Type

Article

Disciplines

Cancer Biology | Cell Biology | Cellular and Molecular Physiology | Molecular Biology

Abstract

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.

Rights and Permissions

Copyright : © 2016 Recouvreux et al. Citation: Oncotarget. 2016 Feb 9;7(6):6552-65. doi: 10.18632/oncotarget.6771. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Keywords

Runx1, Foxp3, Rspo3, GJA1, gene expression regulation

PubMed ID

26735887

Creative Commons License

Creative Commons Attribution 3.0 License
This work is licensed under a Creative Commons Attribution 3.0 License.

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