Nectin cell adhesion molecule-4 (NECTIN-4): A potential target for cancer therapy

NECTIN-4 [a poliovirus receptor-related-4 (pvrl-4) encoded protein] is a Ca2+ independent immunoglobulin-like protein. Along with other Nectins (Nectin-1, -2 and -3), it is primarily involved in cell-cell adhesion. In contrast to other Nectins, Nectin-4 is specifically enriched in the embryonic and placental tissues but its expression significantly declines in adult life. In recent years, it has been found that Nectin-4 is especially overexpressed and served as a tumor associated inducer in various malignant tumors including breast, lung, colorectal, pancreatic, ovarian cancers etc. Over-expression of Nectin-4 is associated with various aspects of tumor progression like proliferation, angiogenesis, epithelial to mesenchymal transition, metastasis, DNA repair, tumor relapse, poor prognosis in several types of cancer. This review systematically highlights the implications of Nectin-4 in every possible aspect of cancer and the molecular mechanism of Nectin-4 mediated cancer progression. We have further emphasized on the therapeutic strategies that are being proposed to specifically target Nectin-4.