Plasma membrane ion fluxes and NFAT-dependent gene transcription contribute to c-met-induced epithelial scattering
| Autor: | Marc D.H. Hansen, Lance Keyes, Peter R. Langford |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Epithelial-Mesenchymal Transition
C-Met Transcription Genetic Cell TRPV Cation Channels Microtubules Receptor tyrosine kinase Madin Darby Canine Kidney Cells TRPC6 Small Molecule Libraries chemistry.chemical_compound Dogs Transcription (biology) medicine Animals Ion channel TRPC Cation Channels Ions NFATC Transcription Factors biology Hepatocyte Growth Factor Cell Membrane Reproducibility of Results Epithelial Cells NFAT Cell Biology Proto-Oncogene Proteins c-met Actins Cell biology medicine.anatomical_structure chemistry biology.protein Calcium Hepatocyte growth factor Signal Transduction medicine.drug |
| Zdroj: | Journal of Cell Science. |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.098269 |
| Popis: | Hepatocyte growth factor (HGF) signaling drives epithelial cells to scatter by breaking cell-cell adhesions and causing them to migrate as solitary cells, a process that parallels epithelial-mesenchymal transition. HGF binds and activates the c-met receptor tyrosine kinase, but downstream signaling required for scattering remains poorly defined. We have applied a chemical biology approach to identify components of HGF signaling that are required for scattering in an in vitro model system. This approach yields a number of small molecules that block HGF-induced scattering, including a calcium channel blocker. We show that HGF stimulation results in sudden and transient increases in ion channel influxes at the plasma membrane. Although multiple channels occur in the membranes of our model system, we find that TrpC6 is specifically required for HGF-induced scattering. We further demonstrate that HGF-induced ion influxes through TrpC6 channels coincide with a transient increase in nuclear factor of activated T-cells (NFAT)-dependent gene transcription and that NFAT-dependent gene transcription is required for HGF-induced cell scattering. |
| Databáze: | OpenAIRE |
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