State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 116000, China.
J Mol Med (Berl). 2018 Apr;96(3-4):265-279. doi: 10.1007/s00109-017-1618-1. Epub 2018 Jan 11.
Lymph node metastasis (N classification) is one of the most important prognostic factors of nasopharyngeal carcinoma (NPC), and nerve involvement is associated with the transition of the N category in NPC patients. Although the nervous system has been reported to participate in many types of cancer progression, its functions in NPC progression remains unknown. Through analysis of gene profiling data, we demonstrate an enrichment of genes associated with neuronal development and differentiation in NPC tissues and cell lines. Among these genes, Nogo receptor 3 (NgR3), which was originally identified in the nervous system and plays a role in nerve development and regeneration, was inappropriately overexpressed in NPC cells and tissues. Immunohistochemical analysis demonstrated that the overexpression of NgR3 was correlated with poor prognosis in NPC patients. Overexpression of NgR3 promoted, and knocking down NgR3 inhibited, NPC cell migration and invasion in vitro and metastasis in vivo. The ability of NgR3 to promote cell migration was triggered by the downregulation of E-cadherin and enhanced cytoskeletal rearrangement and cell polarity, which were correlated with the activation of focal adhesion kinase (FAK). Collectively, NgR3 is a novel indicator of poor outcomes in NPC patients and plays an important role in driving the progression of NPC. These results suggest a potential link between the nervous system and NPC progression.
Genes involved in the neuronal biological process are enriched in nasopharyngeal carcinoma. Overexpression of NgR3 correlates with poor prognosis of nasopharyngeal carcinoma. NgR3 promotes NPC cell migration by downregulating E-cadherin. NgR3 promotes NPC cell polarity and enhances the formation of NPC cell pseudopodia by activating FAK/Src pathway.
淋巴结转移（N 分类）是鼻咽癌（NPC）最重要的预后因素之一，神经侵犯与 NPC 患者 N 类别的转变有关。尽管神经系统已被报道参与多种类型的癌症进展，但它在 NPC 进展中的作用尚不清楚。通过基因谱数据分析，我们在 NPC 组织和细胞系中证明了与神经元发育和分化相关的基因富集。在这些基因中，最初在神经系统中发现的神经生长抑制因子受体 3（NgR3）在 NPC 细胞和组织中过度表达，在神经发育和再生中发挥作用。免疫组织化学分析表明，NgR3 的过表达与 NPC 患者的不良预后相关。NgR3 的过表达促进了 NPC 细胞的迁移和侵袭，以及体内转移，而 NgR3 的敲低则抑制了 NPC 细胞的迁移和侵袭。NgR3 促进细胞迁移的能力是通过下调 E-钙黏蛋白和增强细胞骨架重排和细胞极性触发的，这与粘着斑激酶（FAK）的激活相关。总之，NgR3 是 NPC 患者预后不良的一个新指标，在驱动 NPC 进展中起着重要作用。这些结果提示神经系统与 NPC 进展之间存在潜在联系。
涉及神经元生物学过程的基因在鼻咽癌中富集。NgR3 的过表达与鼻咽癌的不良预后相关。NgR3 通过下调 E-钙黏蛋白促进 NPC 细胞迁移。NgR3 通过激活 FAK/Src 通路促进 NPC 细胞极性，并增强 NPC 细胞伪足的形成。
