Oncotarget

Research Papers:

RUNX1 and FOXP3 interplay regulates expression of breast cancer related genes

María Sol Recouvreux, Esteban Nicolás Grasso, Pablo Christian Echeverria, Luciana Rocha-Viegas, Lucio Hernán Castilla, Carolina Schere-Levy, Johanna Melisa Tocci, Edith Claudia Kordon and Natalia Rubinstein _

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Oncotarget. 2016; 7:6552-6565. https://doi.org/10.18632/oncotarget.6771

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Abstract

María Sol Recouvreux1,6, Esteban Nicolás Grasso1,7, Pablo Christian Echeverria5, Luciana Rocha-Viegas1,2, Lucio Hernán Castilla4, Carolina Schere-Levy1, Johanna Melisa Tocci1, Edith Claudia Kordon1,3, Natalia Rubinstein1,2

1Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE-UBA-CONICET), Buenos Aires, Argentina

2Departamento de Fisiología y Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, UBA, Buenos Aires, Argentina

3Departamento de Química Biológica, UBA, Buenos Aires, Argentina

4Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA

5Department of Biologie Cellulaire, Universite de Geneve Sciences III, Geneve, Switzerland

6Present Address: Oncology Institute “Angel H Roffo”, Buenos Aires, Argentina

7Present Address: Immunopharmacology Laboratory, IQUIBICEN-CONICET, FCEN-UBA, Buenos Aires, Argentina

Correspondence to:

Natalia Rubinstein, e-mail: nrubinstein@fbmc.fcen.uba.ar

Keywords: Runx1, Foxp3, Rspo3, GJA1, gene expression regulation

Received: June 08, 2015     Accepted: November 28, 2015     Published: December 28, 2015

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.


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