Elevated EGFL6 modulates cell metastasis and growth via AKT pathway in nasopharyngeal carcinoma.

Elevated EGFL6 modulates cell metastasis and growth via AKT pathway in nasopharyngeal carcinoma.
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EGFL6 升高通过 AKT 通路调节鼻咽癌细胞转移和生长

DOI:
10.1002/cam4.1883
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发表时间:
2018-12
期刊:
影响因子:
4
通讯作者:
You Y
You Y
中科院分区:
医学3区
文献类型:
--
作者:
Zhu Z;Ni H;You B;Shi S;Shan Y;Bao L;Duan B;You Y

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类表皮生长因子结构域6(EGFL6)是一种分泌蛋白,可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,与正常组织相比,20例鼻咽癌组织中EGFL6高表达。然后,通过酶联免疫吸附试验和蛋白质印迹法检测鼻咽癌血清和鼻咽癌细胞中EGFL6的水平,结果与免疫组化一致。更有趣的是,在体外实验中,EGFL6加速了鼻咽癌的迁移和生长。考虑到迁移机制,用AKT激活剂培养鼻咽癌细胞,结果显示EGFL6通过AKT促进鼻咽癌的进展。此外,在裸鼠中证实了EGFL6促进鼻咽癌生长的相同作用。进一步地,建立了EGFL6过表达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增强了鼻咽癌的迁移和转移。目前,由于鼻咽癌的预后受到远处转移的严重影响,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在鼻咽癌的迁移和增殖中可能是一个潜在的正向调节因子。
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.
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