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RUNX1 and FOXP3 interplay regulates expression of breast cancer related genes.

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.

SUBMITTER: Recouvreux MS

PROVIDER: S-EPMC4872732 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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RUNX1 and FOXP3 interplay regulates expression of breast cancer related genes.

Recouvreux María Sol MS Grasso Esteban Nicolás EN Echeverria Pablo Christian PC Rocha-Viegas Luciana L Castilla Lucio Hernán LH Schere-Levy Carolina C Tocci Johanna Melisa JM Kordon Edith Claudia EC Rubinstein Natalia N

Oncotarget 20160201 6

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 physica ...[more]

PMID: 26735887

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Dataset Information

RUNX1 and FOXP3 interplay regulates expression of breast cancer related genes.

Publications

RUNX1 and FOXP3 interplay regulates expression of breast cancer related genes.

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