β-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 β‐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 β‐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. © 2007 Wiley‐Liss, Inc.