Involvement of c-Met/hepatocyte growth factor pathway in cholangiocarcinoma cell invasion and its therapeutic inhibition with small interfering RNA specific for c-Met

Background. Hepatocyte growth factor receptor (c-Met) plays an important role in many functions of cancer cells. We examined the roles of c-Met and its downstream signaling molecules in cholangiocarcinoma cell lines RMCCA1 and HuCCA1. Materials and methods. The expression of c-Met and their signaling cascades were determined in RMCCA1 and HuCCA1 cholangiocarcinoma cell lines by Western blotting. Small interfering RNA (siRNA) specific for c-Met was used to suppress the expression of c-Met. The proliferation, migration and invasion assay were tested in these cholangiocarcinoma cells treated with hepatocyte growth factor (HGF). Results. Activation of c-Met with HGF triggered the signaling via the ERK cascade mediated by sequential phosphorylation of MEK1/2 and MAPK and induction of cholangiocarcinoma cell invasion. The expression of c-Met in cholangiocarcinoma cells was suppressed by treatment with small interfering RNA (siRNA) specific for c-Met, and resulted in decrease in phosphorylation of MEK1/2. Furthermore, treatment with siRNA specific for c-Met or MEK inhibitor U0126 inhibited cholangiocarcinoma cell invasion induced by HGF. Conclusions. These results indicated that HGF and c-Met involved in the mechanism of cholangiocarcinoma cell invasion. It implies a potential role for the inhibition of c-Met in the treatment of cholangiocarcinoma. (c) 2006 Elsevier Inc. All rights reserved.