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

EPHA6致敏BMP-2诱导的胶质母细胞瘤细胞凋亡。将BMP-2和EPHA6过表达的细胞接种到裸鼠脑内，显示出肿瘤抑制导致更长的存活，这与TCGA患者的数据分析一致。通过EPHA6激酶失活突变体K757R和BMP受体抑制剂LDN193189的检测，协同诱导细胞凋亡的作用依赖于BMP I型受体的激酶活性，但不依赖于EPHA6激酶的功能。最后，RNA测序结果表明，在EPHA6过度表达的细胞中，凋亡相关基因表达上调，可能有重要的下游靶基因有待进一步研究。手稿已经提交，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.