Runx1 and Foxp3 interplay regulates expression of breast cancer related genes

MARIA SOL RECOUVREUX; ESTEBAN N. GRASSO,; PABLO C. ECHEVERRIA; LUCIANA ROCHA VIEGAS; LUCIO H. CASTILLA,; CAROLINA SCHERE-LEVY; JOHANA M. TOCCI; EDITH C. KORDON,; NATALIA RUBINSTEIN.

Oncotarget

Impact Journals, LLC

Año: 2015

Runx1 participation in epithelial mammary cells is still under review. Emergingdata indicates that Runx1 could be relevant for breast tumor promotion.However, to date no studies have specifically evaluated the functionalcontribution of Runx1 to control gene expression in mammary epithelial tumorcells. It has been described that Runx1 activity is defined by protein contextinteraction. Interestingly, Foxp3 is a breast tumor suppressor gene. Here weshow that endogenous Runx1 and Foxp3 physically interact in normalmammary 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 bindingupregulates Rspo3 oncogene expression and downregulates GJA1 tumorsuppressor gene expression in a Foxp3-dependent manner. Moreover,reduced Runx1 transcriptional activity decreases tumor cell migrationproperties. Collectively, these data provide evidence of a new mechanism forbreast tumor gene expression regulation, in which Runx1 and Foxp3physically interact to control mammary epithelial cell gene expression fate.Our work suggests for the first time that Runx1 could be involved in breasttumor progression depending on Foxp3 availability.