The Protrusive Phase and Full Development of Integrin-Dependent Adhesions in Colon Epithelial Cells Require FAK- and ERK-Mediated Actin Spike Formation: Deregulation in Cancer Cells1
| Autor: | Brunton, Valerie G, Fincham, Valerie J, McLean, Gordon W, Winder, Steven J, Paraskeva, Christos, Marshall, John F, Frame, Margaret C |
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| Jazyk: | angličtina |
| Rok vydání: | 2001 |
| Předmět: |
Adenoma
Integrins MAP Kinase Signaling System Mice Nude Mice Antigens Neoplasm Tumor Cells Cultured Animals Humans Neoplasm Invasiveness Phosphorylation Cell Line Transformed Mitogen-Activated Protein Kinase Kinases Focal Adhesions Receptor Protein-Tyrosine Kinases Epithelial Cells Protein-Tyrosine Kinases Actins Fibronectins Up-Regulation Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases Colonic Neoplasms Disease Progression Cell Adhesion Molecules Research Article |
| Popis: | Integrins play an important role in tumour progression by influencing cellular responses and matrix-dependent adhesion. However, the regulation of matrix-dependent adhesion assembly in epithelial cells is poorly understood. We have investigated the integrin and signalling requirements of cell-matrix adhesion assembly in colon carcinoma cells after plating on fibronectin. Adhesion assembly in these, and in the adenoma cells from which they were derived, was largely dependent on alpha v beta 6 integrin and required phosphorylation of FAK on tyrosine-397. The rate of fibronectin-induced adhesion assembly and the expression of both alpha v beta 6 integrin and FAK were increased during the adenoma-to-carcinoma transition. The matrix-dependent adhesion assembly process, particularly the final stages of complex protrusion that is required for optimal cell spreading, required the activity of extracellular signal-regulated kinase (ERK). Furthermore, phosphorylated ERK was targeted to newly forming cell--matrix adhesions in the carcinoma cells but not the adenoma cells, and inhibition of FAK--tyrosine-397 phosphorylation or MEK suppressed the appearance of phosphorylated ERK at peripheral sites. In addition, inhibition of MEK--ERK activation blocked the formation of peripheral actin microspikes that were necessary for the protrusive phase of cell-matrix adhesion assembly. Thus, MEK--ERK--dependent peripheral actin re-organization is required for the full development of integrin-induced adhesions and this pathway is stimulated in an in vitro model of colon cancer progression. |
| Databáze: | OpenAIRE |
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