Netrin receptor UNC5B (UNC5B)

Netrin receptor UNC5B is a transmembrane protein belonging to the UNC5 family, characterized as a dependence receptor that regulates cell survival based on ligand availability. In the presence of its primary ligand, Netrin-1, UNC5B provides survival signals; however, in the absence of Netrin-1, the receptor is cleaved by caspases to induce apoptosis [UniProt: Q8IZJ1]. This mechanism is a critical tumor-suppressive pathway that is often bypassed in various cancers through the overexpression of Netrin-1, which prevents UNC5B-mediated cell death [PubMed: 24507156]. Beyond oncology, UNC5B plays a pivotal role in the vascular system by acting as a repulsive receptor for Netrin-1 to control endothelial tip cell guidance and vessel branching [PubMed: 15510150]. It also functions in the immune system by inhibiting the migration of leukocytes, thereby acting as an endogenous anti-inflammatory signal [PubMed: 19116665]. Therapeutic development focuses on using monoclonal antibodies like NP137 to disrupt the Netrin-1/UNC5B interaction, effectively re-engaging the apoptotic program in malignant cells [PubMed: 37532831]. Consequently, UNC5B represents a versatile target for treating advanced solid tumors and potentially managing pathological angiogenesis.

Other names

UNC5H2Protein unc-5 homolog Bp53-regulated receptor for death and life protein 1p53RDL1

Blockade of the Netrin-1/UNC5B interaction using monoclonal antibodies to trigger the dependence receptor-mediated apoptotic pathway in cancer cells [PubMed: 37532831].