PURPOSE: Uveal melanoma is the most common primary intraocular malignancy in 
adult humans. Unlike cutaneous melanoma, uveal melanoma disseminates 
preferentially to the liver through the hematogenous system. To date, the 
mechanism underlying this metastatic homing is largely unknown. This study 
investigated the effect of hepatocyte growth factor (HGF)-triggered signaling 
pathways to identify the role of HGF and its downstream effectors in inducing 
the migration of uveal melanoma cells.
METHODS: Migration of uveal melanoma cells was measured by in vitro wound 
healing and transwell migration assays. The expression and translocation of 
c-Met were detected using indirect immunofluorescence. The activation of 
extracellular signal-regulated kinase (ERK)1/2 and phosphatidylinositol 3-kinase 
(PI3K)/protein kinase B (Akt) pathways was analyzed using specific antibodies 
against phospho-ERK1/2 and phospho-Akt. The impact of HGF treatment on the 
expression of cell adhesion molecules was measured using Western blotting.
RESULTS: HGF was found to enhance cell migration, and that HGF-induced migration 
depends on PI3K/Akt pathway. The activation of PI3K/Akt pathway induced by the 
HGF/c-Met axis is involved in the downregulation of cell adhesion molecules 
E-cadherin and beta-catenin, contributing to the attenuation of cell-cell 
adhesion and promoting the enhanced motility and migration of uveal melanoma 
cells. On HGF stimulation, receptor c-Met is translocated to the nucleus in a 
ligand-dependent manner, suggesting that c-Met may modulate the expression of 
genes involved in melanoma cell migration.
CONCLUSIONS: Data from this study directly linked the central PI3K/Akt pathway 
to uveal melanoma migration and pointed to new avenues for therapeutic 
intervention in hepatic metastasis.