Department of Otorhinolaryngology - Head and Neck Surgery, School of Medicine, Konkuk University, Seoul, South Korea.
Department of Otorhinolaryngology - Head and Neck Surgery, College of Medicine, Hallym University, Seoul, South Korea.
Neoplasma. 2020 Mar;67(2):259-266. doi: 10.4149/neo_2019_190313N220. Epub 2019 Nov 26.
Nasopharyngeal carcinoma (NPC) is a rare form of the head and neck cancer of the epithelial lining of the nasopharynx and exhibits the highest metastatic rate among head and neck cancers. Underlying mechanisms of metastasis remain largely unknown. Here, we explored whether Notch1 affects the invasion and metastasis of NPC cells. In vitro migration and invasion capacities were evaluated after the knockdown of Notch1 expression in NPC cells. To investigate the role of Notch1 in in vivo metastasis, we examined the metastatic ability to the lungs following administration of cancer cells via mouse tail vein. The expression of epithelial-mesenchymal transition (EMT) markers associated with Notch1-mediated metastasis was investigated, and their roles in metastasis and relationship with Notch1 expression were investigated. Suppression of Notch1 expression increased the ability of NPC cells to invade Matrigel in vitro. Knockdown of Notch1 expression in NPC cells resulted in extensive lung metastasis in a mouse model and increased the mRNA expression of Slug in NPC cells. Slug-specific RNA interference resulted in the loss of the metastatic and invasion capacities in Notch1-suppressed NPC cells. These findings show that Notch1 has a significant suppressive role in the regulation of metastasis in NPCs, suggestive of its prudent use in clinical trials.
鼻咽癌（NPC）是一种罕见的头颈部癌症，发生于鼻咽部上皮衬里，其转移率在头颈部癌症中最高。转移的潜在机制在很大程度上尚不清楚。在这里，我们探讨了 Notch1 是否影响 NPC 细胞的侵袭和转移。敲低 NPC 细胞中的 Notch1 表达后，评估了体外迁移和侵袭能力。为了研究 Notch1 在体内转移中的作用，我们通过尾静脉注射癌细胞来检查向肺部转移的能力。研究了与 Notch1 介导的转移相关的上皮-间充质转化（EMT）标志物的表达，并研究了它们在转移中的作用及其与 Notch1 表达的关系。抑制 Notch1 表达可增加 NPC 细胞体外侵袭 Matrigel 的能力。在 NPC 细胞中敲低 Notch1 表达会导致小鼠模型中广泛的肺转移，并增加 NPC 细胞中 Slug 的 mRNA 表达。Slug 特异性 RNA 干扰导致 Notch1 抑制的 NPC 细胞丧失转移和侵袭能力。这些发现表明 Notch1 在 NPC 转移的调节中具有显著的抑制作用，提示在临床试验中谨慎使用。
