Following these results, we here demonstrate that Ephrin B3 and EphA2 are concomitantly expressed in NSCLC cells of different histology and that blocking Ephrin B3 expression inhibits cell proliferation, migration and invasion in vitro. By immunoprecipitation and proximity ligation assay (PLA) in situ we for the first time show that Ephrin B3 interacts with EphA2 and other EphAs e.g. EphA3, EphA4 and EphA5. This evidence concerns the gene EFNB3 and non-small cell lung carcinoma.