胶质细胞系源性神经营养因子（GDNF）能促进胶质瘤细胞迁移。研究发现，胶质瘤细胞膜上存在大量无粘附能力的神经钙粘素前体（pro-N-cad）,这是胶质瘤细胞迁移的主要原因，而pro-N-cad增加是成对碱性氨基酸蛋白酶(furin)减少所致。我们前期研究显示，GDNF能与pro-N-cad相互作用，故此，我们认为，GDNF促胶质瘤细胞迁移是经pro-N-cad介导、激活一条细胞内信号通路、下调furin表达，进而产生更多pro-N-cad而实现的。为验证该正反馈环路的存在，本项目拟研究在GDNF作用下，pro-N-cad/β-catenin复合体上β-catenin的脱落；胞核内β-catenin/CDX2/TCF复合体的形成；CDX2与furin基因启动子结合量下降等系列因素致furin基因表达下调。该项目的完成能为深入了解胶质瘤细胞迁移提供理论依据，并为防治胶质瘤转移提供新思路。

Glial cell-line Derived Neurotrophic Factor (GDNF) can promote glioma cells to metastasize. Recent publications suggest increased levels of the non-adhesive transmembrane pre-protein, proN-cadherin, is the main reason why glioma cells are prone to metastasis. Further research has found that the increase of pro-N-cadherin in glioma cells is due to a decreased expression of furin. In our previous research we showed that GDNF and proN-cadherin interact. We believe there is a positive feedback loop in glioma cells that promotes metastasis by overproduction of proN-cadherin. The signaling pathway begins with GDNF and proN-cadherin's interaction. This results in decreased expression of furin and therefore increases production of proN-cadherin in glioma cells. In order to prove and elucidate this positive feedback loop, we plan to demonstrate that β-catenin is released from the pro-N-cad/β-catenin membrane complex when the concentration of GDNF is increased. Once free, cytoplasmic β-catenin can enter the nucleus and form a β-catenin/CDX2/TCF complex. CDX2's sequestration in this complex will keep it from interacting with the promoter of furin gene, which in turn will downregulate its expression. Our research project would provide the mechanistic foundation of metastasis in glioma cells, which will bring new ideas for the clinical treatment of glioma.