Flotillin-2 promotes metastasis of nasopharyngeal carcinoma by activating NF-κB and PI3K/Akt3 signaling pathways.
Flotillin-2 promotes metastasis of nasopharyngeal carcinoma by activating NF-κB and PI3K/Akt3 signaling pathways.
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DOI：
10.1038/srep11614
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发表时间：
2015-07-24
影响因子：
4.6
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Liu J;Huang W;Ren C;Wen Q;Liu W;Yang X;Wang L;Zhu B;Zeng L;Feng X;Zhang C;Chen H;Jia W;Zhang L;Xia X;Chen Y
脂筏蛋白已被证实在细胞信号转导中很重要。一些报告表明，脂筏蛋白的异常表达与某些癌症的恶性表型相关。然而，脂筏蛋白flotillin-2 (Flot-2)在鼻咽癌(NPC)中的作用仍有待全面表征。本研究通过免疫染色检测鼻咽癌组织和细胞系中Flot-2的过度表达，发现Flot-2表达与鼻咽癌转移呈正相关。此外，抑制Flot-2表达通过限制高转移性NPC细胞系5-8F的生长和增殖、移动性和迁移以及降低5-8F细胞在裸鼠中的转移能力来损害其恶性程度。相反，强制过度表达 Flot-2 会增加 6-10B 的恶性程度，6-10B 是一种弱表达 Flot-2 的非转移性 NPC 细胞系。此外，在抑制Flot-2表达的5-8F-shFlot-2细胞中，NF-κB和PI3K/Akt3通路被失活。随后，MMPs 表达减少，Foxo1 活性增加。此外，在过表达 Flot-2 的 6-10B 细胞中观察到 NF-κB 和 PI3K/Akt3 活性增强。因此，Flot-2在NPC中发挥促肿瘤作用，并参与肿瘤进展和转移。此外，Flot-2 通过 NF-κB 和 PI3K/Akt3 信号传导发挥作用。
Lipid raft proteins have been confirmed to be important in cell signal transduction. Some reports have shown that the aberrant expression of lipid raft proteins is associated with malignant phenotypes in some cancers. However, the role of the lipid raft protein flotillin-2 (Flot-2) in nasopharyngeal carcinoma (NPC) remains to be comprehensively characterized. Here, overexpression of Flot-2 in NPC tissues and cell lines was detected by immunostaining, and Flot-2 expression was found to be positively associated with NPC metastasis. Furthermore, inhibiting Flot-2 expression impaired the malignancy of the highly metastatic NPC cell line 5-8F by constraining its growth and proliferation, mobility and migration, and decreasing the capacity of 5-8F cells to metastasize in nude mice. In contrast, forced overexpression of Flot-2 increased the malignancy of 6-10B, a non-metastatic NPC cell line that weakly expresses Flot-2. Moreover, in 5-8F-shFlot-2 cells, which have inhibited Flot-2 expression, the NF-κB and PI3K/Akt3 pathways were inactivated. Subsequently, MMPs expression were decreased, and Foxo1 activity was increased. In addition, enhanced NF-κB and PI3K/Akt3 activities were observed in Flot-2 overexpressing 6-10B cells. Thus, Flot-2 exerts a pro-neoplastic role in NPC and is involved in tumor progression and metastasis. Moreover, Flot-2 exerts its role through NF-κB and PI3K/Akt3 signaling.