关键词: E-box motif Epithelial-to-Mesenchymal Transition (EMT) Snail Zinc finger domain metastasis transcription factor.

Mesh : A549 Cells Adenocarcinoma, Bronchiolo-Alveolar / genetics pathology Biomarkers, Tumor / genetics Cell Movement / drug effects genetics Codon, Nonsense Epithelial-Mesenchymal Transition / drug effects genetics Gene Expression Regulation, Neoplastic / drug effects genetics Humans Lung Neoplasms / genetics pathology Protein Domains / genetics physiology Protein Isoforms / chemistry genetics pharmacology Snail Family Transcription Factors / chemistry genetics pharmacology physiology Transforming Growth Factor beta1 / pharmacology

来  源:   DOI:10.2174/1574892814666190527111429

Abstract:
BACKGROUND: Epithelial-to-Mesenchymal Transition (EMT) is necessary for metastasis. Zinc- finger domain-containing transcription factors, especially Snail1, bind to E-box motifs and play a crucial role in the induction and regulation of EMT.
OBJECTIVE: We hypothesized if C-terminal region of Snail1 (CSnail1) may competitively bind to E-box and block cancer metastasis.
METHODS: The CSnail1 gene coding sequence was inserted into the pIRES2-EGFP vector. Following transfection of A549 cells with the designed construct, EMT was induced with TGF-β1 and the expression of essential EMT markers was evaluated by real-time PCR and immunoblotting. We also monitored cell migration.
RESULTS: CSnail1 inhibited TGF-β1-induced N-cadherin and vimentin mRNA expression and increased β-catenin expression in transfected TGF-β1-treated A549 cells. A similar finding was obtained in western blotting. CSnail1 also blocked the migration of transfected cells in the scratch test.
CONCLUSIONS: Transfection of A549 cells with CSnail1 alters the expression of essential EMT markers and consequently suppresses tumor cell migration. These findings confirm the capability of CSnail1 in EMT blocking and in parallel to current patents could be applied as a novel strategy in the prevention of metastasis.
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