Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Am J Pathol. 2012 Nov;181(5):1773-81. doi: 10.1016/j.ajpath.2012.07.014. Epub 2012 Sep 11.
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.
鼻咽癌（NPC）的特征是其与 Epstein-Barr 病毒（EBV）的强烈关联和高转移率。最近，在人类癌症和肿瘤转移中发现过表达的 recepteur d'origine nantais（RON）（MST1R），受体酪氨酸激酶。因此，研究了 RON 在 EBV 相关 NPC 及其转移中的作用。在这里，我们发现 RON 存在于 NPC 中，但不存在于对照组织中。在 NPC 中发现了潜伏膜蛋白 1（LMP1）和 RON 表达的显著相关性（Pearson χ(2)检验；P = 0.0023）。在分子水平上，LMP1 通过其羧基末端激活区 1 刺激核因子-κB 与 RON 启动子结合，从而诱导 RON 的表达。在表达 LMP1 的细胞中敲低 RON 可显著逆转 LMP1 诱导的上皮-间充质转化，并抑制 LMP1 诱导的细胞迁移和侵袭。这些结果表明 RON 在 NPC 的肿瘤发生和转移中具有重要作用，RON 可能是 EBV 相关 NPC 的一个新的治疗靶点。
