Characterization of E-cadherin-dependent and -independent events in a new model of c-Fos-mediated epithelial-mesenchymal transition
| Autor: | Marina Kriajevska, J. Kilian Mellon, Igor B. Bronstein, Fedor Berditchevski, Eugene Tulchinsky, Jakob Mejlvang, Eugene Lukanidin, J. Howard Pringle |
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| Rok vydání: | 2006 |
| Předmět: |
Biology
Adenocarcinoma Models Biological Epigenesis Genetic Extracellular matrix Mesoderm Mice Cell Movement Cell Line Tumor Cell Adhesion Mesenchymal–epithelial transition Animals Neoplasm Invasiveness Cell adhesion Promoter Regions Genetic beta Catenin Cell Proliferation Cell adhesion molecule Cadherin Epithelial Cells Cell Biology DNA Methylation Cadherins Molecular biology Cell biology Extracellular Matrix Fibronectin Gene Expression Regulation Neoplastic Catenin Mutation biology.protein Neural cell adhesion molecule Proto-Oncogene Proteins c-fos |
| Zdroj: | Experimental cell research. 313(2) |
| ISSN: | 0014-4827 |
| Popis: | Fos proteins have been implicated in control of tumorigenesis-related genetic programs including invasion, angiogenesis, cell proliferation and apoptosis. In this study, we demonstrate that c-Fos is able to induce mesenchymal transition in murine tumorigenic epithelial cell lines. Expression of c-Fos in MT1TC1 cells led to prominent alterations in cell morphology, increased expression of mesenchymal markers, vimentin and S100A4, DNA methylation-dependent down-regulation of E-cadherin and abrogation of cell-cell adhesion. In addition, c-Fos induced a strong beta-catenin-independent proliferative response in MT1TC1 cells and stimulated cell motility, invasion and adhesion to different extracellular matrix proteins. To explore whether loss of E-cadherin plays a role in c-Fos-mediated mesenchymal transition, we expressed wild-type E-cadherin and two different E-cadherin mutants in MT1TC1/c-fos cells. Expression of wild-type E-cadherin restored epithelioid morphology and enhanced cellular levels of catenins. However, exogenous E-cadherin did not influence expression of c-Fos-dependent genes, only partly suppressed growth of MT1TC1/c-fos cells and produced no effect on c-Fos-stimulated cell motility and invasion in matrigel. On the other hand, re-expression of E-cadherin specifically negated c-Fos-induced adhesion to collagen type I, but not to laminin or fibronectin. Of interest, mutant E-cadherin which lacks the ability to form functional adhesive complexes had an opposite, potentiating effect on cell adhesion to collagen I. These data suggest that cell adhesion to collagen I is regulated by the functional state of E-cadherin. Overall, our data demonstrate that, with the exception of adhesion to collagen I, c-Fos is dominant over E-cadherin in relation to the aspects of mesenchymal transition assayed in this study. |
| Databáze: | OpenAIRE |
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