cAMP-induced Epac-Rap activation inhibits epithelial cell migration by modulating focal adhesion and leading edge dynamics
| Autor: | Wytse Bruinsma, J.H. Raaijmakers, Johan de Rooij, Johannes L. Bos, Karen S. Lyle |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Integrins
Cell biology cell migration Epac Integrin Biology Epithelial cell migration Cell Line Focal adhesion Geneeskunde Dogs Cell Movement cAMP Cyclic AMP Animals Guanine Nucleotide Exchange Factors Humans Small GTPase Pseudopodia Cell adhesion Cytoskeleton Migration Focal Adhesions Hepatocyte Growth Factor Cadherin fungi Epithelial Cells Cell migration Cell Biology body regions Intercellular Junctions rap GTP-Binding Proteins biology.protein sense organs Rap Signal Transduction |
| Zdroj: | Cellular signalling, 20(6), 1104. Elsevier |
| ISSN: | 0898-6568 |
| Popis: | Epithelial cell migration is a complex process crucial for embryonic development, wound healing and tumor metastasis. It depends on alterations in cell-cell adhesion and integrin-extracellular matrix interactions and on actomyosin-driven, polarized leading edge protrusion. The small GTPase Rap is a known regulator of integrins and cadherins that has also been implicated in the regulation of actin and myosin, but a direct role in cell migration has not been investigated. Here, we report that activation of endogenous Rap by cAMP results in an inhibition of HGF- and TGFbeta-induced epithelial cell migration in several model systems, irrespective of the presence of E-cadherin adhesion. We show that Rap activation slows the dynamics of focal adhesions and inhibits polarized membrane protrusion. Importantly, forced integrin activation by antibodies does not mimic these effects of Rap on cell motility, even though it does mimic Rap effects in short-term cell adhesion assays. From these results, we conclude that Rap inhibits epithelial cell migration, by modulating focal adhesion dynamics and leading edge activity. This extends beyond the effect of integrin affinity modulation and argues for an additional function of Rap in controlling the migration machinery of epithelial cells. |
| Databáze: | OpenAIRE |
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