Description
Nectins are a family of type I transmembrane proteins that are involved in a Ca2+-independent immunoglobulin-like cell-cell adhesion molecules consisting of four members, Nectin-1-4. Nectin-4, also known as PVRL4, LNIR or PRR4, is expressed in the embryo and the placenta, whereas the other nectins are expressed widely in human adult tissues. The extracellular domain of nectin-4 is cleaved at the cell surface via the proteolytic activity of ADAM17/TACE, and the soluble form is released into the blood. Increased levels of the circulating form of nectin-4 have been detected in the sera of patients with metastatic breast cancer. The soluble form of nectin-4 has also been detected in significant amounts in the sera of patients with non-small cell lung cancer (NSCLC), and the up-regulation of soluble nectin-4 in the serum has been suggested to be associated with a poor prognosis for NSCLC.
Nectin-4 is overexpressed in a variety of cancers other than the above and is currently under clinical investigation as a therapeutic target. Oncolytic virotherapy is a novel treatment strategy for cancer. Vaccine and laboratory-adapted strains of measles virus (MV) uses nectin-4 and CD46 molecule as major entry receptors into cells. A recombinant measles virus which selectively uses nectin-4 receptor is used in oncolytic agents for cancer. Also anti-nectin-4 antibodies such as enfortumab (AGS-22M6E) are under clinical investigation for cancer therapies. Furthermore mutations in nectin-4 are associated with ectodermal dysplasia-syndactyly syndrome 1 (EDSS1)