Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan, PR China.
Eur J Cancer. 2010 Nov;46(16):2996-3006. doi: 10.1016/j.ejca.2010.07.008. Epub 2010 Aug 13.
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.
主要的 Epstein-Barr 病毒 (EBV) 致癌蛋白潜伏膜蛋白 1 (LMP1) 被认为有助于鼻咽癌 (NPC) 的高度侵袭性。信号转导和转录激活因子 3 (STAT3) 是增殖和凋亡的主要转录调节因子，新近涉及血管生成和侵袭性，这反过来可能有助于 NPC 的高度侵袭性特征。LMP1 调节 NPC 细胞侵袭中 STAT3 激活的基本分子机制尚未完全探索。在这里，我们表明 LMP1 在激活 STAT3 时信号转导子和转录激活子 3 (JAK3) 和细胞外信号调节激酶 1/2 (ERK1/2) 途径，以及 STAT 反式激活活性。LMP1 通过 JAK/STAT 和丝裂原活化蛋白激酶 (MAPK)/ERK 信号通路诱导血管内皮生长因子 (VEGF) 的表达。人类病毒致癌蛋白 LMP1 诱导 STAT3 的产生可能有助于 NPC 的侵袭。
