beta-Catenin and actin reorganization in HGF/SF response of ST14A cells.
Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic factor that activates proliferation, differentiation, and migration of various cell types. Its action is mediated by c-Met, a receptor endowed with tyrosine kinase activity that activates complex signaling cascades and mediates diverse cell responses. Although HGF action was first demonstrated in epithelial cells, expression of HGF and c-Met receptor has also been described in developing and adult mammalian brain. In the developing central nervous system, areas of HGF and c-Met expression are coincident with the migratory pathway of precursor cells. In the present article we report that the interaction between c-Met and HGF/SF in striatal progenitor ST14A cells triggers a signaling cascade that induces modification of cell morphology, with decreased cell-cell interactions and increased cell motility; in particular, we analyzed the reorganization of the actin cytoskeleton and the delocalization of beta-catenin and N-cadherin. The testing of other neurotrophic factors (NGF, BDNF, NT3, and CNTF) showed that the observed modifications were peculiar to HGF. We show that phosphoinositide 3-kinase inhibitor treatment, which blocks cell scattering induced by HGF/SF, does not abolish actin and beta-catenin redistribution. The effects of HGF/SF on primary spinal cord cell cultures were also investigated, and HGF/SF was found to have a possible motogenic effect on these cells. The data reported suggest that HGF could play a role in the early steps of neurogenesis as a motogenic factor.
Soldati
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Dipartimento di Biologia Cellulare e dello Sviluppo, Università di Roma "La Sapienza," Roma, Italy.
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Poiana
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Augusti-Tocco
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D000199:Actins / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017228:Hepatocyte Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019859:Proto-Oncogene Proteins c-met / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D000199:Actins; D015820:Cadherins; D004791:Enzyme Inhibitors; D017228:Hepatocyte Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019859:Proto-Oncogene Proteins c-met; D051176:beta Catenin