Epithelial-mesenchymal transition (EMT) is a key step during tumor progression and dissemination. N-cadherin and VE-cadherin are expressed in mouse mammary tumor cells (Ep5ExTu cells) that have undergone EMT and present a mesenchymal phenotype. Furthermore, VE-cadherin expression in this cell line promotes tumor progression by altering the TGF-beta signaling pathway. Here, we investigated the reciprocal relationship between N-cadherin and VE-cadherin in promoting tumor progression in Ep5ExTu cells. We found that inhibition of N-cadherin expression by a lentiviral vector system in Ep5ExTu cells significantly decreased VE-cadherin expression. In addition, loss of N-cadherin in a dose-dependent manner induced E-cadherin expression, localized b-catenin to the cell membrane, and decreased SIP1 and vimentin expression, suggesting that N-cadherin silencing induced Ep5ExTu cells to undergo a mesenchymal-(to-) epithelial reverting transition (MErt). Consistent with our in vitro data, efficient downregulation of N-cadherin in Ep5ExTu cells inhibited tumor growth in vivo, suggesting that N-cadherin expression in malignant fibroblastoid tumor cells promotes tumor growth We also observed the re-expression of E-cadherin and downregulation of vimentin in N-cadherin silenced tumors, indicating that silencing N-cadherin by inducing the cells to undergo a MErt prevents tumor progression. In addition, exogenous expression of VE-cadherin in N-cadherin silenced cells that have undergone MErt had no influence on tumor progression; thus N-cadherin has a more significant role than VE-cadherin in promoting tumor growth of cell line. Together our results indicate a novel function for N-cadherin in tumor progression by controlling VE-cadherin expression and reveal the link between N-cadherin silencing and MErt in mouse mammary tumor cells.