Artemin

Artemin (ARTN) is the GDNF family ligand distinguished by its partnership with the co-receptor GFRα3 and the RET receptor tyrosine kinase. Processed from a pre-pro-protein into a secreted homodimeric cystine-knot protein, artemin is produced by non-neuronal tissues-including smooth muscle of blood vessels and gut, Schwann cells, bone marrow stroma and developing skin-and acts retrogradely on the axons of sympathetic and sensory neurons that innervate these targets. Through GFRα3/RET activation of MAPK and PI3K pathways, artemin promotes survival and neurite outgrowth of sympathetic ganglion neurons and a major subpopulation of peptidergic nociceptors, restores damaged peripheral nerves after injury, and reprograms sensory neurons toward a hyperexcitable phenotype. Consequently, artemin is centrally implicated in neuropathic and inflammatory pain sensitization, and anti-artemin strategies have been explored as analgesics. In oncology, artemin drives invasion and migration of pancreatic, breast, esophageal and head-and-neck cancer cells via RET and non-RET mechanisms, and confers resistance to chemo- and radiotherapy in neuroblastoma and glioma models.