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

ABSTRACT: Transcription factor lymphoid-enhancer-binding factor 1 (LEF-1) is a key molecule in the Wnt/?-catenin signaling pathway. Slug is one of the Wnt/?-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 ?-catenin-binding region can induce EMT, suggesting that LEF-1 acts independently of ?-catenin. Because it has been reported that LEF-1 interacts with ?-catenin outside the amino-terminal domain, namely, in the middle part of the molecule, the possible participation of ?-catenin has not been formally ruled out. To determine the involvement of ?-catenin in the LEF-1-induced EMT, we produced MDCK cells with a deletion of the ?-catenin gene and then expressed LEF-1 in the cells. We found that LEF-1 induced EMT in those cells. In the absence of ?-catenin, ?-catenin has been shown to take over the role of ?-catenin. To examine this possibility, we first established MDCK cells with a double knockout of ?-catenin and ?-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 ?-catenin nor ?-catenin expression is necessary for the LEF-1-mediated induction of EMT.

SUBMITTER: Kobayashi W

PROVIDER: S-EPMC6038150 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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

Kobayashi Wakako W Ozawa Masayuki M

Biochemistry and biophysics reports 20180612

Transcription factor lymphoid-enhancer-binding factor 1 (LEF-1) is a key molecule in the Wnt/β-catenin signaling pathway. <i>Slug</i> 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 th ...[more]

PMID: 29998192

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Project description:BackgroundCigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and lung cancer. Epithelial-mesenchymal transition (EMT) is an essential pathophysiological process in COPD and plays an important role in airway remodeling, fibrosis, and malignant transformation of COPD. Previous studies have indicated FERMT3 is downregulated and plays a tumor-suppressive role in lung cancer. However, the role of FERMT3 in COPD, including EMT, has not yet been investigated.MethodsThe present study aimed to explore the potential role of FERMT3 in COPD and its underlying molecular mechanisms. Three GEO datasets were utilized to analyse FERMT3 gene expression profiles in COPD. We then established EMT animal models and cell models through cigarette smoke (CS) or cigarette smoke extract (CSE) exposure to detect the expression of FERMT3 and EMT markers. RT-PCR, western blot, immunohistochemical, cell migration, and cell cycle were employed to investigate the potential regulatory effect of FERMT3 in CSE-induced EMT.ResultsBased on Gene Expression Omnibus (GEO) data set analysis, FERMT3 expression in bronchoalveolar lavage fluid was lower in COPD smokers than in non-smokers or smokers. Moreover, FERMT3 expression was significantly down-regulated in lung tissues of COPD GOLD 4 patients compared with the control group. Cigarette smoke exposure reduced the FERMT3 expression and induces EMT both in vivo and in vitro. The results showed that overexpression of FERMT3 could inhibit EMT induced by CSE in A549 cells. Furthermore, the CSE-induced cell migration and cell cycle progression were reversed by FERMT3 overexpression. Mechanistically, our study showed that overexpression of FERMT3 inhibited CSE-induced EMT through the Wnt/β-catenin signaling.ConclusionsIn summary, these data suggest FERMT3 regulates cigarette smoke-induced epithelial-mesenchymal transition through Wnt/β-catenin signaling. These findings indicated that FERMT3 was correlated with the development of COPD and may serve as a potential target for both COPD and lung cancer.

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

Publications

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

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