Abstract
Transcription factor lymphoid-enhancer–binding factor 1 (LEF-1) is a key molecule in the Wnt/β-catenin signaling pathway. Slug is one of the Wnt/β-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 β-catenin–binding region can induce EMT, suggesting that LEF-1 acts independently of β-catenin. Because it has been reported that LEF-1 interacts with β-catenin outside the amino-terminal domain, namely, in the middle part of the molecule, the possible participation of β-catenin has not been formally ruled out. To determine the involvement of β-catenin in the LEF-1–induced EMT, we produced MDCK cells with a deletion of the β-catenin gene and then expressed LEF-1 in the cells. We found that LEF-1 induced EMT in those cells. In the absence of β-catenin, γ-catenin has been shown to take over the role of β-catenin. To examine this possibility, we first established MDCK cells with a double knockout of β-catenin and γ-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 β-catenin nor γ-catenin expression is necessary for the LEF-1–mediated induction of EMT.
Highlights
Epithelial–mesenchymal transition (EMT) is known as one of the essential steps for tissue remodeling, organ development, wound healing, and cancer metastasis [1,2,3,4]
1 and an amino terminus–deleted mutant lymphoid-enhancer–binding factor 1 (LEF-1), ΔNLEF-1, which cannot interact with β-catenin, has an ability to induce EMT [12]
To determine whether β-catenin is required for induction of LEF1–induced EMT, we disrupted the β-catenin gene using the clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR-associated 9 (Cas9) gene editing system
Summary
Epithelial–mesenchymal transition (EMT) is known as one of the essential steps for tissue remodeling, organ development, wound healing, and cancer metastasis [1,2,3,4]. Members of the lymphoid-enhancer–binding factor 1/T-cell factor (LEF-1/TCF) family are key transcription factors that interact with βcatenin and activate Wnt/β-catenin signaling [5]. We found that the expression of ΔNLEF-1 induces EMT in MDCK cells [12] These observations have suggested that β-catenin is not necessary for the LEF-1–mediated induction of EMT. There is a report that in addition to the well-established amino-terminal β-catenin–binding domain of LEF-1, β-catenin binds to another site of LEF-1: residues 150–175 [13] Because of these findings, the possibility of involvement of β-catenin in EMT induction is a contentious topic. To determine the involvement of β-catenin in LEF-1–induced EMT, we established MDCK cells with disruption of the β-catenin gene using the CRISPR/Cas gene editing system and introduced a LEF-1 expression vector. These results revealed that LEF-1 induces EMT independently of β-catenin and γ-catenin
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