Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
J Neurooncol. 2018 Jul;138(3):469-478. doi: 10.1007/s11060-018-2818-4. Epub 2018 Mar 8.
As an important member of the Annexins, AnnexinA5 has been attributed important functions in trophoblast membrane repair, anticoagulation and cellular signal transduction. Accumulated studies show that AnnexinA5 is closely associated with various types of carcinomas. However, the potential contribution of AnnexinA5 to glioma cancer progression remains unclear. In this study, we report that AnnexinA5 is significantly upregulated in both high-grade glioma samples and glioma cell lines. Moreover, overexpression of AnnexinA5 promotes cell migration and invasion in vitro and tumorigenicity of glioma cells in nude mice, while knockdown of AnnexinA5 manifests a repressive function during these cellular processes. Importantly, mechanistic studies further reveal that AnnexinA5 is an essential transcriptional target of Snail via activating the PI3K/Akt/NF-κB signaling pathway. Taken together, these findings suggest that AnnexinA5 or the PI3K/Akt/NF-κB pathway may be promising therapeutic molecules to eradicate glioma metastases.
作为 Annexins 的重要成员之一, AnnexinA5 在滋养层细胞膜修复、抗凝和细胞信号转导中具有重要功能。大量研究表明,AnnexinA5 与各种类型的癌症密切相关。然而,AnnexinA5 对神经胶质瘤癌症进展的潜在贡献尚不清楚。在这项研究中,我们报告 AnnexinA5 在高级别神经胶质瘤样本和神经胶质瘤细胞系中均显著上调。此外,AnnexinA5 的过表达促进了体外细胞迁移和侵袭以及裸鼠中神经胶质瘤细胞的致瘤性,而 AnnexinA5 的敲低在这些细胞过程中表现出抑制作用。重要的是,机制研究进一步表明 AnnexinA5 是 Snail 的一个重要转录靶标,通过激活 PI3K/Akt/NF-κB 信号通路。总之,这些发现表明 AnnexinA5 或 PI3K/Akt/NF-κB 通路可能是根除神经胶质瘤转移的有前途的治疗分子。