Department of Otorhinolaryngology Head and Neck surgery, Affiliated Hospital of Nantong University, Nantong, China.
Cancer Med. 2018 Dec;7(12):6281-6289. doi: 10.1002/cam4.1883. Epub 2018 Nov 15.
Epidermal growth factor-like domain multiple 6 (EGFL6) is a secreted protein, regulates maintenance and metastasis of cancer cells. Nevertheless, how EGFL6 participates in the progression and tumorigenesis of nasopharyngeal carcinoma (NPC) remains unclear. In our study, EGFL6 was detected highly expressed in 20 NPC tissues compared with normal tissues by IHC assay. Then, the level of EGFL6 in NPC serum and NPC cells was explored through enzyme-linked immunosorbent assay and western blot, the results consistent with IHC. More interestingly, EGFL6 accelerated the migration and growth of NPC in vitro assays. Considering the mechanism of migration, NPC cells were cultured with AKT activator, revealing EGFL6 facilitated the progression of NPC via AKT. Moreover, the same effect of EGFL6 in promoting NPC growth was proved in nude mice. Furthermore, heat-shock zebrafish model was established with EGFL6 overexpression. Then, CNE2 cells were injected into the model and cells mass was observed, showing that EGFL6 enhanced the migration and metastasis of NPC. Currently, as the prognosis of NPC is severely affected by distant metastasis, it might be a new therapeutic target toward EGFL6. Taken together, our results suggested that EGFL6 acts as a potential positive regulator in the migration and proliferation of NPC.
表皮生长因子样结构域蛋白 6(EGFL6)是一种分泌蛋白,调节癌细胞的维持和转移。然而,EGFL6 如何参与鼻咽癌(NPC)的进展和肿瘤发生仍不清楚。在我们的研究中,通过免疫组化检测,发现 EGFL6 在 20 例 NPC 组织中高表达,明显高于正常组织。然后,通过酶联免疫吸附试验和 Western blot 检测 NPC 血清和 NPC 细胞中的 EGFL6 水平,结果与 IHC 一致。更有趣的是,EGFL6 加速了 NPC 的体外迁移和生长。考虑到迁移的机制,将 NPC 细胞与 AKT 激活剂一起培养,结果表明 EGFL6 通过 AKT 促进 NPC 的进展。此外,在裸鼠中也证明了 EGFL6 促进 NPC 生长的相同作用。进一步建立了过表达 EGFL6 的热休克斑马鱼模型。然后,将 CNE2 细胞注入该模型并观察细胞团,结果表明 EGFL6 增强了 NPC 的迁移和转移。目前,NPC 的预后严重受远处转移的影响,因此 EGFL6 可能成为一个新的治疗靶点。综上所述,我们的研究结果表明,EGFL6 作为 NPC 迁移和增殖的潜在正调控因子发挥作用。