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Impact of Small Molecules on β-Catenin and E-Cadherin Expression in HPV16-positive and -negative Squamous Cell
Benedikt Kramer1, Clemens Hock2, Johannes David Schultz3
1Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University Heidelberg, Mannheim, Germany benedikt.kramer@umm.de.
Background:
The validation of potential molecular targets in head and neck squamous cell carcinoma (SCC) is mandatory. β-Catenin and E-cadherin are crucial for cancer progression through epithelial-mesenchymal transition. We analyzed the effect of the tyrosine kinase inhibitors nilotinib, dasatinib, erlotinib and gefitinib on β-catenin and E-cadherin expression in SCC with respect to human papillomavirus (HPV) status.
Materials And Methods:
Expression of β-catenin and E-cadherin in cell lines UMSCC 11A, UMSCC 14C and CERV196 under the influence of tyrosine kinase inhibitors were analyzed by enzyme-linked immunosorbent assay.
Results:
All agents reduced β-catenin and E-cadherin expression of HPV16-negative cells. Increased E-cadherin expression was observed after treatment with gefitinib and dasatinib in HPV16-positive cells.
Conclusion:
All substances, nilotinib, dasatinib, erlotinib and gefitinib have a significant impact on β-catenin and E-cadherin expression in both HPV16-positive and HPV16-negative cells in vitro. Alterations of β-catenin and E-cadherin could provide novel insights for future targeted therapies of head and neck SCC.
Insights
Tyrosine kinase inhibitors impact β-catenin and E-cadherin expression in head and neck squamous cell carcinoma (SCC). These findings offer insights for developing targeted therapies for SCC, regardless of human papillomavirus (HPV) status.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Head and neck squamous cell carcinoma (SCC) requires validation of molecular targets.
- β-Catenin and E-cadherin are key in cancer progression via epithelial-mesenchymal transition.
- Human papillomavirus (HPV) status influences SCC characteristics.
Purpose of the Study:
- To investigate the effect of tyrosine kinase inhibitors (nilotinib, dasatinib, erlotinib, gefitinib) on β-catenin and E-cadherin expression in SCC.
- To analyze these effects in relation to HPV status.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) was used to analyze protein expression.
- SCC cell lines (UMSCC 11A, UMSCC 14C, CERV196) were treated with tyrosine kinase inhibitors.
- Experiments were conducted in vitro.
Main Results:
- All tested agents reduced β-catenin and E-cadherin expression in HPV16-negative SCC cells.
- Gefitinib and dasatinib increased E-cadherin expression in HPV16-positive SCC cells.
- Significant impacts on β-catenin and E-cadherin were observed in both HPV16-positive and HPV16-negative cells.
Conclusions:
- Tyrosine kinase inhibitors significantly alter β-catenin and E-cadherin expression in head and neck SCC cells in vitro.
- These molecular alterations may offer novel insights for targeted SCC therapies.
- The study highlights the potential of targeting these proteins for therapeutic strategies in head and neck SCC.
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