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

EPHA 6致敏胶质母细胞瘤细胞用于BMP-2诱导的凋亡。用BMP-2和EPHA 6过表达预处理的细胞接种到裸鼠脑中显示出肿瘤抑制，导致更长的存活期，与TCGA患者数据分析一致。对凋亡诱导的协同作用依赖于BMP I型受体的激酶活性，但与EPHA 6激酶功能无关，如使用EPHA 6激酶失活突变体K757 R和BMP受体抑制剂LDN 193189所测试的。最后，RNA测序结果表明，在EPHA 6过表达的细胞中，前列腺癌相关基因表达上调，这可能是今后研究的重要下游靶基因。稿件已提交，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.