Nectin-3 and Nectin-4: potential prognostic biomarkers for therapeutic targeting of cancer

Abstract

Nectin-3 and nectin-4 belong to the immunoglobulin (Ig) superfamily, and are Ca2+ -independent homophilic cell adhesion molecules.  Nectin-3 is ubiquitous in adult tissues, and it enhances normal levels of synaptic formation. In contrast, nectin-4 is weakly-to-moderately  expressed in normal human tissues. In recent years, studies have shown that nectin-3 is highly expressed in the nervous system. Moreover, it is associated with poor prognostic factors in distant metastases and malignant tumors with high vascular invasion such as  pancreatic, lung and breast cancers. In particular, nectin-4 is overexpressed in various malignant tumors, and it is associated with  proliferation, angiogenesis, metastasis, drug resistance, tumor relapse, DNA repair, cancer stemness, and poor prognosis. Unlike nectin-3, nectin-4 has become a potential prognostic biomarker and specific therapeutic target for cancer as there is no consensus on the  significance of abnormal expression of nectin-3 in various cancers.