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04336nam a2200757Ia 4500 |
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10.1111-jop.13230 |
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220427s2021 CNT 000 0 und d |
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|a 09042512 (ISSN)
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|a Effect of tyrosine kinase inhibitors on cell migration and epithelial-to-mesenchymal transition in Asian head and neck cancer cell lines
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|b John Wiley and Sons Inc
|c 2021
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|z View Fulltext in Publisher
|u https://doi.org/10.1111/jop.13230
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|a Background: We investigated the role of epidermal growth factor (EGF) and transforming growth factor α (TGFα) on Asian head and neck cancer patient cell lines; in terms of epithelial-to-mesenchymal transition (EMT) and cell migration to determine whether these changes could be reversed using tyrosine kinase inhibitors (Gefitinib and Erlotinib). Methods: Cell migration, protrusion and EMT were assessed using both Scatter assay and Scratch assay. Protein expression and localisation were evaluated using immunofluorescence, SDS-PAGE and Western blotting techniques to identify the involvement of phosphorylated MAPK (Thr202/Tyr204), phosphorylated EGFR (Y1068) and phosphorylated AKT (Ser473) protein expression. Results: EGF and TGFα induced an EMT-like phenotypical change, cellular protrusion and cell migration while Gefitinib and Erlotinib blocked these morphological changes and cell migration. We also examined the effect of EGF/TGF α± tyrosine kinase inhibitors on phosphorylation sites Y1068 of epidermal growth factor receptor (EGFR). Y1068 was phosphorylated in all test conditions, and all tested concentrations of inhibitors did not inhibit Y1068 phosphorylation. EGF and TGFα increased phosphorylation of MAPK (Thr202/Tyr204) residues compared with serum-free control while a one-hour pre-treatment with tyrosine kinase inhibitor(s) before addition of growth factors completely blocked this phosphorylation. Phosphorylation of Akt Ser 473 was also induced by EGF and TGFα, and a one-hour pre-treatment with the tyrosine kinas inhibitor(s) reduced this phosphorylation. Conclusion: These data suggest that Gefitinib and Erlotinib prevent activation of downstream signalling proteins MAPK (Thr202/Tyr204) and Akt (Ser473) thereby blocking phenotypic change and cell migration. This study supports the potential therapeutic value of Gefitinib and Erlotinib in targeting head and neck cancer. © 2021 The Authors. Journal of Oral Pathology & Medicine published by John Wiley & Sons Ltd.
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|a Akt signaling
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|a Article
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|a Asian
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|a Asian cell lines
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|a cell line
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|a Cell Line
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|a Cell Line, Tumor
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|a cell migration
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|a cell migration
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|a cell motility
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|a cell motion
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|a Cell Movement
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|a controlled study
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|a down regulation
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|a drug effect
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|a EGFR signaling
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|a epidermal growth factor
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|a epidermal growth factor
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|a Epidermal Growth Factor
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|a epidermal growth factor receptor
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|a epidermal growth factor receptor
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|a epithelial mesenchymal transition
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|a epithelial-to-mesenchymal transition
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|a erlotinib
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|a gefitinib
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|a HaCat cell line
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|a head and neck cancer cell line
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|a Head and Neck Neoplasms
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|a head and neck tumor
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|a HSG cell line
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|a human
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|a human cell
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|a Humans
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|a immunofluorescence
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|a MAPK signaling
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|a mitogen activated protein kinase
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|a polyacrylamide gel electrophoresis
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|a protein expression
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|a protein function
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|a protein kinase B
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|a protein kinase inhibitor
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|a Protein Kinase Inhibitors
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|a protein phosphorylation
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|a signal transduction
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|a Signal Transduction
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|a transforming growth factor alpha
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|a tumor cell line
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|a tyrosine
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|a Western blotting
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|a wound healing assay
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|a Ellis, I.R.
|e author
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|a Mossey, P.
|e author
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|a Thwe, A.M.
|e author
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|t Journal of Oral Pathology and Medicine
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