EphB1, an erythropoietin-producing hepatoma (Eph) receptor tyrosine kinase, mediates bidirectional signaling upon binding to membrane-bound ephrin ligands. It plays crucial roles in multiple biological processes including cell migration, adhesion, differentiation, proliferation, and survival. EphB1/ephrin signaling is involved in the development of the central nervous system, immune organs, and regulation of synapse formation and maturation [1].

In cancer, EphB1 shows paradoxical roles. In colorectal cancer, mutations in EphB1 impair its kinase-dependent tumor-suppressor function, reducing its activity, stability, and the ability to suppress cell migration [2]. In non-small cell lung cancer, EphB1 promotes the differentiation and maturation of dendritic cells [3]. In acute myelogenous leukemia, EphB1 restoration activates the DNA damage response cascade, suggesting a tumor-suppressor function [5]. In NSCLC, EphB1 cis-and trans-signalings regulate cancer stem cells enrichment after chemotherapy [6]. In the nervous system, EphB1 in GABAergic neurons is required for proper cortical axon guidance during brain development, as EphB1 conditional knockout in these cells (Vgat-Cre) recapitulates the axon guidance defects seen in global EphB1 KO mice [4].

In conclusion, EphB1 is essential for normal development and tissue homeostasis, with its dysregulation contributing to various diseases, especially cancer. Studies using gene knockout and conditional knockout mouse models have been instrumental in revealing its role in cancer progression, immune cell regulation, and nervous system development, providing potential targets for therapeutic intervention.