Membrane glycoprotein nectin-4 in tumor associated pathways and anti-cancer therapeutics

Nectin-4, a cell adhesion molecule (CAM) of the immunoglobulin superfamily of proteins, has recently gained prominence as a tumor-associated antigen. Although, primarily considered as a cell adhesion glycoprotein involved in embryonic development, its enhanced expression in various types of cancers and its negligible presence in healthy adult tissues makes it a potent target for developing anti-cancer therapeutics. Moreover, the extracellular portion of nectin-4 is shed off by the action of matrix metalloproteinases, which leads to its presence in the blood of cancer patients, thereby making it a serological cancer marker that can be targeted for diagnostic purposes. This review discusses the role of nectin-4 in several pathophysiological aspects of cancer progression by linking these to the molecular mechanistic details of cell-signaling pathways. Moreover, it also provides very intricate categorical documentation and analysis of the expression pattern of nectin-4 in various forms of cancer. It further emphasizes on the therapeutic approaches targeting nectin-4, thus depicting the importance of this protein in basic and clinical cancer research. This review also extends its scope of discussion beyond cancer biology by presenting the involvement of nectin-4 in embryonic development and infectious diseases to provide a holistic significance of this protein in human health and diseases.