Branched N‐glycans regulate the biological functions of integrins and cadherins

Abstract

Glycosylation is one of the most common post‐translational modifications, and approximately 50% of all proteins are presumed to be glycosylated in eukaryotes. Branched N‐glycans, such as bisecting GlcNAc, β‐1,6‐GlcNAc and core fucose (α‐1,6‐fucose), are enzymatic products of N‐acetylglucosaminyltransferase III, N‐acetylglucosaminyltransferase V and α‐1,6‐fucosyltransferase, respectively. These branched structures are highly associated with various biological functions of cell adhesion molecules, including cell adhesion and cancer metastasis. E‐cadherin and integrins, bearing N‐glycans, are representative adhesion molecules. Typically, both are glycosylated by N‐acetylglucosaminyltransferase III, which inhibits cell migration. In contrast, integrins glycosylated by N‐acetylglucosaminyltransferase V promote cell migration. Core fucosylation is essential for integrin‐mediated cell migration and signal transduction. Collectively, N‐glycans on adhesion molecules, especially those on E‐cadherin and integrins, play key roles in cell–cell and cell–extracellular matrix interactions, thereby affecting cancer metastasis.