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

2019 Fiscal Year Annual Research Report

• Project/Area Number: 19K16735
• Research Institution: The University of Tokyo
• Principal Investigator: Raja Erna 東京大学, 大学院医学系研究科(医学部), 特任研究員 (30770581)
• Project Period (FY): 2019-04-01 – 2020-03-31
• Keywords: BMP / glioblastoma / apoptosis / EPHA6

Outline of Annual Research Achievements

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.