Metadherin knockdown suppresses bladder cancer cell invasion and metastasis by inhibiting the epithelial to mesenchymal transition

Metadherin is over-expressed in several cancers and it is has been considered as an important oncogene. Recent studies have shown that elevated expression of metadherin is associated with poor prognosis in patients with transitional cell carcinoma, however, the potential role of metadherin in transitional cell carcinoma remains unknown. In this study, Paraffin sections of clinical bladder samples were evaluated by immunohistochemistry, Statistical analyses were applied to test for the relation between MTDH and E-cadherin, and the association of MTDH or E-cadherin with bladder cancer patients’clinicopathlogic features, respectively. After transfected with siRNAs, the expression of metadherin in T24 and 5637 cells were assessed by Real-time reverse transcription-PCR and Western blot. Moreover, the expression of Epithelial-to-mesenchymal transition (EMT)-related markers such as E-cadherin, N-cadherin, Vimentin were detected by Real-time reverse transcription-PCR and Western blot assay. Scratch wound assay and transwell matrix penetration assay were performed to determine migration and invasion of T24 and 5637 cells. We found that metadherin was over-expressed in clinical patients with transitional cell carcinoma, and the expression of metadherin and E-cadherin significantly correlated with Histopathological Grade (WHO, 2004), Clinical stage (UICC, 2002), and distant metastasis. There was a negative correlation between metadherin high expression and E-cadherin low expression in bladder cancer patients. In addition, we revealed that knock down metadherin in bladder cancer cells resulted in decreased regulation of N-cadherin, Vimentin, upregulation of E-cadherin. Furthermore, the siRNA-mediated down-regulation of metadherin resulted in decreased migration and invasion of T24 and 5637 cells. We speculate that MTDH knockdown might suppress migration and invasion in bladder cancer cells through the epithelial to mesenchymal transition.