Nectin-4, also known as poliovirus-like receptor 4 (PVRL4), is a newly discovered cell adhesion molecule, which belongs to the Nectin family. There are four members of the Nectin family: Nectin-1, Nectin-2, Nectin-3 and Nectin-4. There are three continuous immunoglobulin-like domains outside the cells of Nectin protein, which are N-terminal Ig-V domain and C-terminal Ig-C2 domain. Nectin-4 is mainly expressed in placenta, expressed in normal human tissues including skin, bladder, salivary glands, esophagus, breast and stomach, and abnormally expressed on the surface of a variety of cancer cells such as breast cancer, bladder cancer, non-small cell lung cancer and pancreatic cancer. Nectin-4 promotes the proliferation, differentiation, migration and invasion of tumor cells by activating PI3K/Akt pathway. In some cancers, such as urothelial carcinoma, the high expression of Nectin-4 can promote tumor cell proliferation and angiogenesis and reduce cancer cell apoptosis. Some studies have shown that Nectin-4, as a new ligand of TIGIT, can inhibit the activity of natural killer cells. These suggest that Nectin-4 may be a potential target for cancer therapy.
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