EphrinA2 promotes glioma cell migration and invasion through EphA2 and FAK

Cancer Cell Int. 2025 May 24;25(1):191. doi: 10.1186/s12935-025-03826-7.

Abstract

Background: EphrinA2, a ligand of the Eph receptor tyrosine kinase family, is implicated in the malignant phenotypes of various cancer cells. However, its function in glioblastoma remains unclear. Therefore, this study aimed to investigate the function and molecular mechanisms of ephrinA2 in the glioblastoma cells.

Methods: EphrinA2 expression in five glioma cell lines and 40 cases of glioblastoma tissue obtained at surgery was examined. Additionally, we examined the effects of ephrinA2 knockdown in the migration and invasion of glioma cells in vitro and in vivo. Moreover, western blotting was performed to elucidate the mechanisms of ephrinA2 in glioma cell invasion and migration.

Results: QRT-PCR showed that ephrinA2 was highly expressed in T98G and SNB19 cells. EphrinA2 knockdown shortened cell protrusions and reduced the migration and invasion abilities of T98G and SNB19 cells, which was confirmed by time-lapse dynamic observations. Western blotting showed that ephrinA2 knockdown suppressed phosphorylation of FAK at Tyr861 and EphA2 at Ser897 in glioma cells. Moreover, immunohistochemical analysis of glioblastoma samples showed that glioma cell invasion into normal brain was significantly higher in the ephrinA2 high expression group than in the low expression group.

Conclusion: EphrinA2 may be involved in promoting glioblastoma invasion by regulating FAK and EphA2 phosphorylation.

Keywords: EphA; EphrinA; Glioblastoma; Invasion; Migration; ephrinA2.