Netrin-3 (NTN3)

Netrin-3 is a secreted laminin-related protein belonging to the netrin family, involved in guidance of cell migration and axon pathfinding during embryonic development[3]. Structurally, it contains an N-terminal laminin domain, three EGF-like repeat domains, and a conserved C-terminal region. Netrin-3 binds to members of the DCC and UNC5 receptor families—known as "dependence receptors"—where it promotes cell survival and, in its absence, receptor signaling can drive apoptosis[3]. In cancer, netrin-3 is frequently upregulated in tumors of neuroectodermal or neuroendocrine origin, such as neuroblastoma and small cell lung cancer, where it sustains tumor growth, aids survival of dormant cells, and correlates with disease aggressiveness[2][1]. Netrin-3 has been investigated as a therapeutic target; the anti-netrin-1 antibody NP137 has shown activity against netrin-3-expressing tumors in preclinical models and inhibits netrin-3/receptor interactions in vitro and in vivo[2]. Netrin-3 is also referred to as NTN2L or netrin-2-like due to its homology with the chicken netrin-2 ortholog.

Other names

Netrin-2-like proteinNTN2LNetrin-2-likeNetrin-2 chicken homolog-like proteinNet3_HUMAN

Inhibition of netrin-3/receptor interaction (NP137 blocks interaction with UNC5B and DCC dependent receptors) Promotion of apoptosis in tumor cells by blocking survival signaling via dependence receptors