A Truncated Snail1 Transcription Factor Alters the Expression of Essential EMT Markers and Suppresses Tumor Cell Migration in a Human Lung Cancer Cell Line

Author(s): Mohammad Davoodzadeh Gholami, Reza Falak*, Sahel Heidari, Majid Khoshmirsafa, Mohammad H. Kazemi, Amir-Hassan Zarnani, Elaheh Safari, Nader Tajik, Gholam A. Kardar*.

Journal Name: Recent Patents on Anti-Cancer Drug Discovery

Volume 14 , Issue 2 , 2019

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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.

Conclusion: 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.

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

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VOLUME: 14
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Year: 2019
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DOI: 10.2174/1574892814666190527111429
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