Involvement of Recepteur d'Origine Nantais Receptor Tyrosine Kinase in Epstein-Barr Virus-Associated Nasopharyngeal Carcinoma and Its Metastasis

Abstract

Nasopharyngeal carcinoma (NPC) is characteristic for its strong association with Epstein-Barr virus (EBV) and high metastatic rate. Recently, overexpressed recepteur d'origine nantais (RON) (MST1R), receptor tyrosine kinase has been reported in human cancers and tumor metastasis. Therefore, the role of RON in EBV-associated NPC and its metastasis was investigated. Here we show that RON was found in NPC but not in control tissues. A significant correlation of latent membrane protein 1 (LMP1) and RON expression was found in NPC (Pearson's χ(2) test; P = 0.0023). At the molecular level, LMP1 stimulates nuclear factor-κB binding to the RON promoter through its carboxyl-terminal activation region 1 to induce expression of RON. Knockdown of RON in cells expressing LMP1 significantly reverses LMP1-induced epithelial-mesenchymal transition and suppresses LMP1-induced cell migration and invasion. These results suggest an important role of RON in the tumorigenesis and metastasis of NPC and RON may be a novel therapeutic target for EBV-associated NPC.