Suppression of Met expression by RNA interference inhibits the metastatic potential of nasopharyngeal carcinoma cells

Abstract

Objective: To investigate the effects of Met overexpression on the invasive phenotype of nasopharyngeal carcinoma (NPC), and to assess downstream signaling pathways mediated by hepatocyte growth factor (HGF). Methods: The NPC cell line CNE-2 was used as an in vitro model to examine the influence of Met overexpression in regulating cell invasion and migration. Met expression was knockdown by using Met specific siRNA, cell invasion was examined by a Matrigel invasion assay and in vitro migration was measured by the transwell migration assay. Results: Met downregulation by siRNA reduced the invasion-motile response to HGF. Treatment of the cells with specific inhibitors against Akt (LY294002) and JNK (SP600125) or expression of their dominant negative forms abolished HGF-stimulated cell invasion, associated with downregulation of matrix metalloproteinases-9. Conversely, the inhibition by ERK1/2 and p38 MAPK had no effect. Conclusions: Met overexpression may play an important role in the progression and metastasis of NPC by activating the Akt and JNK pathways, and raise the possibility of their application for cancer therapy.