Epstein‐Barr virus‐encoded latent membrane protein 1 promotes extracellular vesicle secretion through syndecan‐2 and synaptotagmin‐like‐4 in nasopharyngeal carcinoma cells

• Published in: Cancer science Vol. 111; no. 3; pp. 857 - 868
• Main Authors: Liao, Chaoliang, Zhou, Qin, Zhang, Zhibao, Wu, Xia, Zhou, Zhuan, Li, Bo, Peng, Jinwu, Shen, Liangfang, Li, Dan, Luo, Xiangjian, Yang, Lifang
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.03.2020; John Wiley and Sons Inc
• Subjects: Animals; Cell adhesion & migration; Cell culture; Cell growth; Cell interactions; Cell Line, Tumor; Cell Movement - physiology; Cell proliferation; Cell Proliferation - physiology; Epstein-Barr virus; extracellular vesicle; Extracellular Vesicles - metabolism; Female; Gene Expression Regulation, Neoplastic - physiology; Heat shock proteins; Herpesvirus 4, Human - metabolism; Humans; Latent membrane protein 1; LMP1; Membrane proteins; Metastases; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Nasopharyngeal carcinoma; Nasopharyngeal Carcinoma - metabolism; Nasopharyngeal Neoplasms - metabolism; NF-kappa B - metabolism; Original; Protein expression; SDC2; Secretion; Signal Transduction - physiology; Synaptotagmin; Syndecan; Syndecan-2 - metabolism; SYTL4; Transmission electron microscopy; Tumors; Up-Regulation - physiology; Vesicular Transport Proteins - metabolism; Viral Matrix Proteins - metabolism; China; LMP1; nasopharyngeal carcinoma; SYTL4; extracellular vesicle; SDC2
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.14305

Increasing evidence indicates that extracellular vesicles (EVs) play an important role in cancer cell‐to‐cell communication. The Epstein‐Barr virus (EBV)‐encoded latent membrane protein 1 (LMP1), which is closely associated with nasopharyngeal carcinoma (NPC) pathogenesis, can trigger multiple cell signaling pathways that affect cell progression. Several reports have shown that LMP1 promotes EV secretion, and LMP1 trafficking by EVs can enhances cancer progression and metastasis. However, the molecular mechanism by which LMP1 promotes EV secretion is not well understood. In the present study, we found that LMP1 promotes EV secretion by upregulated syndecan‐2 (SDC2) and synaptotagmin‐like‐4 (SYTL4) through nuclear factor (NF)‐κB signaling in NPC cells. Further study indicated that SDC2 interacted with syntenin, which promoted the formation of the EVs, and SYTL4 is associated with the release of EVs. Moreover, we found that stimulation of EV secretion by LMP1 can enhance the proliferation and invasion ability of recipient NPC cells and tumor growth in vivo. In summary, we found a new mechanism by which LMP1 upregulates SDC2 and SYTL4 through NF‐κB signaling to promote EV secretion, and further enhance cancer progression of NPC. We found a new mechanism by which latent membrane protein 1 upregulated syndecan‐2 and synaptotagmin‐like‐4 through nuclear factor‐kB signaling to promote exosome secretion, and further enhance cancer progression of nasopharyngeal carcinoma.