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Supplementary Figure 2 from Novel Role of MDA-9/Syntenin in Regulating Urothelial Cell Proliferation by Modulating EGFR Signaling

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posted on 2023-03-31, 17:13 authored by Santanu Dasgupta, Mitchell E. Menezes, Swadesh K. Das, Luni Emdad, Aleksandar Janjic, Shilpa Bhatia, Nitai D. Mukhopadhyay, Chunbo Shao, Devanand Sarkar, Paul B. Fisher

PDF file - 621K, Supplementary Figure S2: Immunofluorescence analysis of EGFR and C-Src (Y418) expression in MDA-9/syntenin-depleted T24 cells

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ARTICLE ABSTRACT

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