EphA6 tyrosine kinase as a potential biomarker for BMP-based therapy in adult glioblastoma

EPHA6致敏bmp -2诱导胶质母细胞瘤细胞凋亡。将BMP-2和EPHA6过表达预处理的细胞接种到裸鼠脑中，显示肿瘤抑制导致存活时间延长，与TCGA患者数据分析一致。采用EPHA6激酶失活突变体K757R和BMP受体抑制剂LDN193189进行实验，结果表明，诱导凋亡的协同效应依赖于BMP I型受体的激酶活性，而不依赖于EPHA6激酶的功能。EPHA6还与ALK-2 BMP受体形成蛋白复合物。最后，rna测序结果表明，凋亡相关基因在EPHA6过表达的细胞中上调，具有潜在的重要下游靶基因，值得进一步研究。稿子已交稿，正在修改中。

EPHA6 sensitized glioblastoma cells for BMP-2-induced apoptosis. Inoculation of cells pre-treated with BMP-2 and EPHA6 over-expression into nude mice brain showed tumor suppression leading to longer survival, in agreement with TCGA patient data analysis.The cooperative effect on apoptosis induction depended on the kinase activity of BMP type I receptor but was independent of EPHA6 kinase function, as tested using EPHA6 kinase inactive mutant K757R and BMP receptor inhibitor LDN193189. EPHA6 also formed a protein complex with ALK-2 BMP receptor.Finally, RNA-sequencing results suggested that apoptosis-associated genes are up-regulated in EPHA6 over-expressing cells with potentially important downstream target genes for further study. The manuscript has been submitted and is being revised.