The epithelial-mesenchymal transition induced by transcription factor LEF-1 is independent of beta-catenin

Transcription factor lymphoid-enhancer-binding factor 1 (LEF-1) is a key molecule in the Wnt/beta-catenin signaling pathway. Slug is one of the Wnt/beta-catenin target genes and can induce epithelial-mesenchymal transition (EMT). Previously, we have shown that not only wild-type LEF-1 but also LEF-1 lacking the amino-terminal beta-catenin-binding region can induce EMT, suggesting that LEF-1 acts independently of beta-catenin. Because it has been reported that LEF-1 interacts with beta-catenin outside the amino-terminal domain, namely, in the middle part of the molecule, the possible participation of beta-catenin has not been formally ruled out. To determine the involvement of beta-catenin in the LEF-1-induced EMT, we produced MDCK cells with a deletion of the beta-catenin gene and then expressed LEF-1 in the cells. We found that LEF-1 induced EMT in those cells. In the absence of beta-catenin, gamma-catenin has been shown to take over the role of beta-catenin. To examine this possibility, we first established MDCK cells with a double knockout of beta-catenin and gamma-catenin genes and then expressed LEF-1 in these cells. We found that LEF-1 can induce EMT in these cells; therefore, we conclude that neither beta-catenin nor gamma-catenin expression is necessary for the LEF-1-mediated induction of EMT.