Bauer, Karin and Dowejko, Albert and Bosserhoff, A. -K. and Reichert, T. E. and Bauer, Richard Josef (2009) P-cadherin induces an epithelial-like phenotype in oral squamous cell carcinoma by GSK-3beta-mediated Snail phosphorylation. CARCINOGENESIS, 30 (10). pp. 1781-1788. ISSN 0143-3334, 1460-2180
Full text not available from this repository. (Request a copy)Abstract
Cadherins belong to a family of Ca2+-dependent homophilic cell-cell adhesion proteins that are important for correct cellular localization and tissue integrity. They play a major role in the development and homeostasis of epithelial architecture. Recently, it has become more and more evident that P-cadherin contributes to the oncogenesis of many tumors. To analyze the role of P-cadherin in oral squamous cell carcinoma (OSCC), we used a cell line that was deficient of the classical cadherins, P-cadherin, E-cadherin and N-cadherin. This cell line was transfected with full-length P-cadherin (PCI52_PC). After overexpression of P-cadherin, PCI52_PC gained an epithelial-like brickstone morphology in contrast to the mock-transfected cells with a spindle-shaped mesenchymal morphology. Immunohistochemical analysis revealed a strong nuclear Snail staining in mock-transfected cells compared with a significantly reduced nuclear staining and translocation to the cytoplasm in P-cadherin-overexpressing cells. Interestingly, the effects triggered by P-cadherin overexpression could be reversed by transfecting the cells with an antisense P-cadherin plasmid construct. Additional investigations showed a reexpression of E-cadherin in all P-cadherin-transfected cell clones in contrast to the mock controls. Analyzing the signaling mechanism behind it, we found glycogen-synthase-kinase-3beta (GSK-3beta) bound to Snail in all cell clones. Furthermore, P-cadherin-overexpressing cell lines showed activated GSK-3beta that phosphorylated Snail leading to its cytoplasmic translocation. In summary, our results reveal P-cadherin as one major component in reconfiguring mesenchymal cells with epithelial features by triggering GSK-3beta-mediated inactivation and cytoplasmatic translocation of Snail in OSCC.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GLYCOGEN-SYNTHASE KINASE-3; MESENCHYMAL TRANSITION; BETA-CATENIN; MALIGNANT-MELANOMA; PROSTATE-CANCER; EXPRESSION; PROGRESSION; TRANSCRIPTION; INVASION; ADHESION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Mund-, Kiefer- und Gesichtschirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 03 Sep 2020 12:31 |
| Last Modified: | 03 Sep 2020 12:31 |
| URI: | https://pred.uni-regensburg.de/id/eprint/28305 |
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