Nectins and nectin-like molecules: roles in contact inhibition of cell movement and proliferation

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Abstract
Nectins and nectin-like molecules (Necls) have recently emerged as cell adhesion molecules that have a variety of cellular functions, including cell movement, proliferation, differentiation, polarization and survival, as well as cell–cell adhesion. The nectin–afadin complex that localizes at adherens junctions (AJs) has a crucial role in the formation of not only cadherin-based AJs but also claudin-based tight junctions (TJs) in epithelial cells. However, it remains unclear how nectins and afadin participate in the positioning of TJs, which are always formed at the apical side of AJs, in epithelial cells. The activation of integrin αvβ3 and its downstream signalling molecules is necessary for the nectin-induced formation of AJs; in turn, integrin αvβ3 is inactivated by the trans-interaction of nectins after the establishment of AJs, indicating that nectins and integrin αvβ3 are involved in the crosstalk between cell–cell and cell–matrix junctions during the formation of AJs. NECL-5, one of the members of the Necl family, significantly promotes cell movement and proliferation in cooperation with the PDGF receptor and integrin αvβ3, but NECL-5 is downregulated from the cell surface after NECL-5 interacts with nectin-3 at the primordial intercellular adhesion sites. This downregulation reduces cell movement and proliferation, indicating the primary involvement of NECL-5 in the contact inhibition of cell movement and proliferation. The expression of NECL-5 is upregulated in cancer cells and this upregulation is correlated with the increased metastatic ability of cancer cells.