STAT3 activation induced by Epstein-Barr virus latent membrane protein1 causes vascular endothelial growth factor expression and cellular invasiveness via JAK3 And ERK signaling

• Published in: European journal of cancer (1990) 2010-11, Vol.46 (16), p.2996-3006
• Main Authors: Wang, Zhenlian, Luo, Feijun, Li, Lili, Yang, Lifang, Hu, Duosha, Ma, Xiaoqian, Lu, Zhongxin, Sun, Lunquan, Cao, Ya
• Format: Article
• Language: English
• Subjects: Angiogenesis; Biological and medical sciences; Blotting, Western; Cell Line, Tumor; Epstein-Barr virus; Extracellular signal-regulated kinase 1/2; Hematology, Oncology and Palliative Medicine; Humans; Invasion ability; Janus Kinase 3; Latent membrane protein 1; Medical sciences; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Nasopharyngeal carcinoma; Nasopharyngeal Neoplasms - metabolism; Nasopharyngeal Neoplasms - pathology; Neoplasm Invasiveness; PD98059; Pharmacology. Drug treatments; RNA, Small Interfering - metabolism; Signal transducer and activator of transcription 3; STAT3 Transcription Factor - metabolism; Transfection; Tumors; Vascular endothelial growth factor; Vascular Endothelial Growth Factors - biosynthesis; Vascular Endothelial Growth Factors - metabolism; Viral Matrix Proteins - antagonists & inhibitors; Viral Matrix Proteins - physiology; WHI-P131
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2010.07.008

Abstract The principal Epstein–Barr virus (EBV) oncoprotein, latent membrane protein 1 (LMP1), has been suggested to contribute to the highly invasive nature of nasopharyngeal carcinoma (NPC). Signal transducer and activator of transcription 3 (STAT3) is a master transcriptional regulator in proliferation and apoptosis and is newly implicated in angiogenesis and invasiveness, which, in turn, are likely to contribute to the highly invasive character of NPC. The fundamental molecular mechanisms of LMP1-regulated STAT3 activation in NPC cell invasion have not been completely explored. Here, we showed that LMP1 signals the Janus kinase 3 (JAK3) and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways upon the activation of STAT3 as well as STAT transactivation activity. LMP1 induces vascular endothelial growth factor (VEGF) expression via the JAK/STAT and mitogen-activated protein kinase (MAPK)/ERK signalling pathways. Induction of STAT3 by the human viral oncoprotein LMP1 may contribute to the invasion of NPC.