脑红蛋白通过EGFR/PI3K/AKT/mTOR-自噬对胶质母细胞瘤侵袭的作用

The distinguishing pathologic features of Glioblastoma multiforme (GBM), such as microvascular hyperplasia and highly invasive, are correlated with abnormal energy metabolism. Neuroglobin (Ngb), a neuronal- or brain-specific respiratory protein, which is highly expressed in GBM. Ngb is up-regulation by hypoxia suggests that Ngb serves as an oxygen sensor in GBM. The role and mechanism of Ngb in GBM is uncertain. Our preliminary results find that Ngb binding with EGFR directly is related with autophagy in GBM, which indicates hypoxia regulates Ngb through EGFR/PI3K/AKT/mTOR-autophagy. Aims of this study: 1) signaling pathway “Ngb-EGFR/PI3K/AKT/mTOR-autophagy” in GBM cell line; 2) the binding regional or sites of Ngb and EGFR; 3) the signaling pathway involving in the invasion of GBM.cells. These results will provide new ideas for treatment of GBM.

胶质母细胞瘤(Glioblastoma multiforme, GBM)的主要病理特征是微血管增生和高侵袭性，均与缺氧密切相关。脑红蛋白（neuroglobin,Ngb）是新型的脑特异氧感受蛋白，在GBM高表达。缺氧诱导Ngb表达增多提示Ngb在GBM细胞中感受缺氧信号。Ngb在GBM中的作用和机制还不确定。预实验发现Ngb与GBM细胞自噬相关且与癌基因EGFR蛋白直接结合，提示Ngb通过EGFR偶联缺氧信号与EGFR/PI3K/AKT/mTOR-自噬信号通路。本项目拟在GBM细胞：1）确证“Ngb-EGFR/PI3K/AKT/mTOR-自噬”这一信号通路；2）确定Ngb与EGFR的结合区域或位点；3）体内外明确这一信号通路对GBM细胞侵袭的作用。结果将为GBM的治疗提供新思路。