远处转移是鼻咽癌治疗失败的主要原因。上皮-间充质转化（EMT）的发生是肿瘤转移的关键环节。近年来，有研究表明外泌体参与EMT的发生及肿瘤转移。但是，在鼻咽癌中还未有外泌体内成分与EMT及侵袭转移的深入研究。我们前期预实验对比鼻咽癌远处转移和非远处转移患者血浆外泌体中的差异表达蛋白，发现M2BP在远处转移患者血浆外泌体中高表达，并与患者远处转移密切相关；体内外实验证明M2BP可促进鼻咽癌细胞EMT及迁移侵袭；RNA测序结果显示M2BP激活NF-κB信号通路且上调下游IL-6的表达；生物信息学分析预测M2BP与IL-6存在相互作用。我们因此提出科学假说：M2BP激活NF-κB信号通路，上调下游IL-6的表达，IL-6与M2BP形成正反馈环路，诱导鼻咽癌细胞EMT，促进鼻咽癌细胞转移。本项目的完成将有助于阐明M2BP促进鼻咽癌转移的新机制，为新药研发以及制定防治鼻咽癌转移的新策略提供理论依据。

Distant metastasis is the major cause of treatment failure in nasopharyngeal carcinoma (NPC). Epithelial-mesenchymal translation (EMT) plays a critical role in tumor invasion and metastasis. In recent years, compelling evidence have shown that exosomes are involved in the occurrence of EMT and tumor metastasis. However, the effects of exosomes on EMT and tumor metastasis remain largely unknown. We performed a quantitative analysis of proteins in plasma-derived exosomes between metastatic and non-metastatic NPC patients to find out the key differential expression proteins. Among them, the expression of M2BP protein was significantly upregulated in plasma-derived exosomes of metastatic NPC patients. We further found that the high-expression of M2BP was related with poorer distant metastasis-free survival of the NPC patients. Our preliminary experiments showed that M2BP could promote the migratory and invasive abilities, as well as the epithelial-mesenchymal translation (EMT) of NPC cells. RNA sequencing analyses found that NF-κB signaling pathway and the expression of downstream target IL-6 was dramatically activated by M2BP. Bioinformatics analyses showed that there may be interaction between M2BP and IL-6. We therefore propose a hypothesis that overexpression of M2BP activates the NF-κB signaling pathway, promotes the expression of IL-6 and forms a positive feedback loop between M2BP and IL-6 to induce EMT and promote NPC metastasis. The accomplishment of the proposed study will reveal a novel mechanism of promoting NPC metastasis via activation of M2BP upon NF-κB signaling pathway and its downstream target IL-6, which could be a potential target for NPC prevention and treatment.