Hong C.-C.Chen P.-S.Chiou J.Chiu C.-F.CHING-YAO YANGHsiao M.Chang Y.-W.Yu Y.-H.Hung M.-C.Hsu N.-W.Shiah S.-G.Hsu N.-Y.Su J.-L.2020-02-202020-02-2020140008-5472https://www.scopus.com/inward/record.uri?eid=2-s2.0-84909594668&doi=10.1158%2f0008-5472.CAN-14-0524&partnerID=40&md5=adf5d7602f89ae036c8a65a6358615b1https://scholars.lib.ntu.edu.tw/handle/123456789/461747Esophageal cancer is an aggressive human malignancy with increasing incidence in the developed world. 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 properties of esophageal squamous cell carcinoma in vitro and tumor metastasis in vivo. Mechanistic investigations showed that VEGF-C increased CTTN expression by downregulating Dicer-mediated maturation of miR326, thereby relieving the suppressive effect of miR326 on CTTN expression. Clinically, expression of Dicer and miR326 correlated with poor prognosis in patients with esophageal cancer. Our findings offer insights into how VEGF-C enhances the robust invasive and metastatic properties of esophageal cancer, which has potential implications for the development of new biomarkers or therapies in this setting. ? 2014 American Association for Cancer Research.[SDGs]SDG3cortactin; dicer; microRNA; microRNA 326; unclassified drug; vasculotropin C; cortactin; microRNA; MIRN326 microRNA, human; tumor marker; vasculotropin C; animal experiment; animal model; animal tissue; Article; cancer growth; cancer prognosis; cell migration; controlled study; esophagus cancer; female; human; human cell; human tissue; in vitro study; in vivo study; major clinical study; male; metastasis; molecular pathology; mouse; nonhuman; protein expression; protein function; cell transformation; disease course; esophagus tumor; gene expression regulation; genetics; metabolism; pathology; prognosis; squamous cell carcinoma; tumor cell line; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Transformation, Neoplastic; Cortactin; Disease Progression; Esophageal Neoplasms; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Prognosis; Tumor Markers, Biological; Vascular Endothelial Growth Factor Cjournal article10.1158/0008-5472.CAN-14-0524252051062-s2.0-84909594668