Ets-1 enhances tumor migration through regulation of CCR7 expression

BMB Rep. 2019 Sep;52(9):548-553. doi: 10.5483/BMBRep.2019.52.9.232.

Abstract

Ets-1 is a prototype of the ETS protein family. Members of the ETS protein family contain a unique ETS domain. Ets-1 is associated with cancer progression and metastasis in many types of cancer. Many studies have shown a link between elevated expression of Ets-1 in cancer biopsies and poor survival. CCR7 is a chemokine that binds to specific ligand CCL21/CCL19. CCR7 expression is associated with tumor metastasis and infiltration into lymph nodes. The objective of this study was to test whether Ets-1 could regulate CCR7 expression and enhance tumor metastasis. Our data showed that CCR7 expression was downregulated in Ets-1-deficient T cells upon T-cell stimulation. Overexpression of Ets-1 increased CCR7 expression in breast cancer cell lines. In contrast, knockdown of Ets-1 reduced CCR7 expression. Ets-1 could directly bind to CCR7 promoter and mediate CCR7 expression in luciferase reporter assays and chromatin immunoprecipitation assays. Transactivation activity of Ets-1 was independent of the Pointed domain of Ets-1. Ets-1 could also enhance NF-κB and CBP transactivation of CCR7 promoter. Our results also showed that Ets-1 could modulate cancer cell transmigration by altering CCR7 expression in transwell assay and wound healing assay. Taken together, our data suggest that Ets-1 can enhance CCR7 expression and contribute to tumor cell migration. [BMB Reports 2019; 52(9): 548-553].

Publication types

  • News

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Chemokine CCL19 / genetics
  • Chemokine CCL19 / metabolism
  • Chemokine CCL21 / genetics
  • Chemokine CCL21 / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • NF-kappa B / metabolism
  • Proto-Oncogene Protein c-ets-1 / genetics
  • Proto-Oncogene Protein c-ets-1 / metabolism*
  • Receptors, CCR7 / genetics*
  • Receptors, CCR7 / metabolism*
  • Signal Transduction / genetics
  • Signal Transduction / physiology

Substances

  • CCL19 protein, human
  • CCL21 protein, human
  • Chemokine CCL19
  • Chemokine CCL21
  • ETS1 protein, human
  • NF-kappa B
  • Proto-Oncogene Protein c-ets-1
  • Receptors, CCR7