Novel function of E26 transformation-specific domain-containing protein ELK3 in lymphatic endothelial cells.

Lymphatic endothelial cells (LEC) are major components of the tumor microenvironment and, due to the relative leakiness of lymphatic vessels compared with blood vessels, are essential for tumor dissemination and metastasis. In the present study, small interfering RNA-mediated suppression of E26 transformation-specific domain-containing protein Elk-3 (ELK3) inhibited the proliferation, migration and tube-forming ability of LEC. Suppression of ELK3 decreased vascular endothelial-cadherin expression levels and increased the phosphorylation of β-catenin. Furthermore, vascular endothelial growth factor receptor-3 (VEGFR-3) mRNA and protein expression levels were suppressed by the transfection of LEC with siELK3. As VEGFR-3 serves a major role in lymphangiogenesis, ELK3 may be a novel therapeutic target to inhibit tumor dissemination through the lymphatic system.