Abstract

 

Ets-1 is a prototype of the ETS protein family, the members of which contain a unique ETS domain. Ets-1 is associated with cancer progression and metastasis in many types of cancer. In many studies, the elevated expression of Ets-1 in cancer biopsies has been linked to poor survival. CCR7 is a chemokine that binds to the specific ligand CCL21/CCL19. CCR7 expression is associated with tumor metastasis and infiltration into lymph nodes. In this study, we tested whether Ets-1 could regulate CCR7 expression and enhance tumor metastasis. Our data show that CCR7 expression is downregulated in Ets-1-deficient T cells upon T-cell stimulation. The overexpression of Ets-1 increases CCR7 expression in breast cancer cell lines. In contrast, the knockdown of Ets-1 reduces CCR7 expression. Ets-1 directly binds to the CCR7 promoter and mediates CCR7 expression in luciferase reporter assays and chromatin immunoprecipitation assays. The transactivation activity of Ets-1 is independent of the Pointed domain of Ets-1. Ets-1 also enhances the NF-B and CBP transactivation of the CCR7 promoter. Finally, we show that Ets-1 can modulate cancer cell transmigration by altering CCR7 expression in a transwell assay and wound healing assay. Taken together, our data suggest that Ets-1 enhances CCR7 expression and contributes to tumor cell migration.