Esophageal cancer is an aggressive human malignancy with rising incidence in the developed world. The vascular endothelial growth factor VEGF-C makes crucial contributions to esophageal cancer progression that are not well understood. Here we report the discovery of regulatory relationship in esophageal cancers between the expression of VEGF-C and cortactin (CTTN), a regulator of the cortical actin cytoskeleton. Upregulation of CTTN expression by VEGF-C enhanced the invasive propertis of esophageal squamous cell carcinoma (ESCC) in vitro and tumor metastasis in vivo. Mechanistic investigations showed that VEGF-C increased CTTN expression by downregulating Dicer-mediated maturation of miR-326, thereby relieving the suppressive effect of miR-326 on CTTN expression. Clinically, expression of Dicer and miR-326 correlated with poor prognosis in esophageal cancer patients. Our findings offer insights into how VEGF-C enhances the robust invasive and metastatic properties of esophageal cancer, which potential implications for the development of new biomarkers or therapies in this setting.
