Versican is a large extracellular chondroitin sulfate proteoglycan that belongs to the family of lecticans. Alternativesplicing of versican generates at least four isoforms named V0, V1, V2, and V3. We show here that ectopic expression ofversican V1 isoform induced mesenchymal-epithelial transition (MET) in NIH3T3 fibroblasts, and inhibition of endogenousversican expression abolished the MET in metanephric mesenchyme. MET in NIH3T3 cells was demonstrated bymorphological changes and dramatic alterations in both membrane and cytoskeleton architecture. Molecular analysisshowed that V1 promoted a "switch" in cadherin expression from N-to E-cadherin, resulting in epithelial specificadhesion junctions. V1 expression reduced vimentin levels and induced expression of occludin, an epithelial-specificmarker, resulting in polarization of V1-transfected cells. Furthermore, an MSP (methylation-specific PCR) assay showedthat N-cadherin expression was suppressed through methylation of its DNA promoter. Exogenous expression of Ncadherinin V1-transfected cells reversed V1’s effect on cell aggregation. Reduction of E-cadherin expression by Snailtransfection and siRNA targeting E-cadherin abolished V1-induced morphological alteration. Transfection of an siRNAconstruct targeting versican also reversed the changed morphology induced by V1 expression. Silencing of endogenousversican prevented MET of metanephric mesenchyme. Taken together, our results demonstrate the involvement ofversican in MET: expression of versican is sufficient to induce MET in NIH3T3 fibroblasts and reduction of versicanexpression decreased MET in metanephric mesenchyme.