A Truncated Snail1 Transcription Factor Alters the Expression of Essential EMT Markers and Suppresses Tumor Cell Migration in a Human Lung Cancer Cell Line.
A549 Cells
Adenocarcinoma, Bronchiolo-Alveolar
/ genetics
Biomarkers, Tumor
/ genetics
Cell Movement
/ drug effects
Codon, Nonsense
Epithelial-Mesenchymal Transition
/ drug effects
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Lung Neoplasms
/ genetics
Protein Domains
/ genetics
Protein Isoforms
/ chemistry
Snail Family Transcription Factors
/ chemistry
Transforming Growth Factor beta1
/ pharmacology
E-box motif
Epithelial-to-Mesenchymal Transition (EMT)
Snail
Zinc finger domain
metastasis
transcription factor.
Journal
Recent patents on anti-cancer drug discovery
ISSN: 2212-3970
Titre abrégé: Recent Pat Anticancer Drug Discov
Pays: United Arab Emirates
ID NLM: 101266081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
24
10
2018
revised:
08
05
2019
accepted:
24
05
2019
pubmed:
28
5
2019
medline:
12
2
2020
entrez:
28
5
2019
Statut:
ppublish
Résumé
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. We hypothesized if C-terminal region of Snail1 (CSnail1) may competitively bind to E-box and block cancer metastasis. 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. 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. 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.
Sections du résumé
BACKGROUND
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
OBJECTIVE
We hypothesized if C-terminal region of Snail1 (CSnail1) may competitively bind to E-box and block cancer metastasis.
METHODS
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
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
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.
Identifiants
pubmed: 31131753
pii: PRA-EPUB-98622
doi: 10.2174/1574892814666190527111429
doi:
Substances chimiques
Biomarkers, Tumor
0
Codon, Nonsense
0
Protein Isoforms
0
SNAI1 protein, human
0
Snail Family Transcription Factors
0
Transforming Growth Factor beta1
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
158-169Informations de copyright
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