Novel Role of MDA-9/Syntenin in Regulating Urothelial Cell Proliferation by Modulating EGFR Signaling

摘要: Purpose: Urothelial cell carcinoma (UCC) rapidly progresses from superficial to muscle-invasive tumors. The key molecules involved in metastatic progression and its early detection require clarification. present study defines a seminal role of the metastasis-associated gene MDA-9/Syntenin UCC progression. Experimental Design: Expression pattern was examined 44 primary impact overexpression knockdown multiple cells lines findings were validated Results: Significantly higher ( P = 0.002–0.003) expression observed 64% (28 44) tumors an association evident with stage 0.01), grade 0.03), invasion status 0.02). nontumorigenic HUC-1 increased proliferation 0.0012), 0.0001), EGF receptor (EGFR), AKT, phosphoinositide 3-kinase (PI3K), c-Src expression. Alteration β-catenin, E-cadherin, vimentin, claudin-1, ZO-1, T-cell factor-4 (TCF4) also observed. three reversed phenotypic molecular changes reduced vivo metastasis. Key confirmed A physical interaction colocalization EGFR logistic regression model analysis revealed significant correlation between MDA-9/Syntenin:EGFR MDA-9/Syntenin:AKT expressions 0.04, EGFR; 0.01, AKT). MDA-9/Syntenin:β-catenin coexpression 0.03) 0.04) evident. Conclusions: Our indicate that might provide attractive target for developing detection, monitoring, therapeutic strategies managing UCC. Clin Cancer Res; 19(17); 4621–33. ©2013 AACR .