Title:A Truncated Snail1 Transcription Factor Alters the Expression of Essential EMT Markers and Suppresses Tumor Cell Migration in a Human Lung Cancer Cell Line
Volume: 14
Issue: 2
Author(s): Mohammad Davoodzadeh Gholami, Reza Falak*, Sahel Heidari, Majid Khoshmirsafa, Mohammad H. Kazemi, Amir-Hassan Zarnani, Elaheh Safari, Nader Tajik and Gholam A. Kardar*
Affiliation:
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran,Iran
- Immunology Asthma & Allergy Research Institute, Children's Medical Center, Tehran University of Medical Sciences, Tehran,Iran
Keywords:
E-box motif, Epithelial-to-Mesenchymal Transition (EMT), metastasis, Snail, transcription factor, Zinc finger domain.
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.
