Aberrant N-glycosylation in cancer: MGAT5 and β1,6-GlcNAc branched N-glycans as critical regulators of tumor development and progression

Background: Changes in protein glycosylation are widely observed in tumor cells. N-glycan branching through adding β1,6-linked N-acetylglucosamine (β1,6-GlcNAc) to an α1,6-linked mannose, which is catalyzed by the N-acetylglucosaminyltransferase V (MGAT5 or GnT-V), is one of the most frequently observed tumor-associated glycan structure formed. Increased levels of this branching structure play a pro-tumoral role in various ways, for example, through the stabilization of growth factor receptors, the destabilization of intercellular adhesion, or the acquisition of a migratory phenotype.

Conclusion: In this review, we provide an updated and comprehensive summary of the physiological and pathophysiological roles of MGAT5 and β1,6-GlcNAc branched N-glycans, including their regulatory mechanisms. Specific emphasis is given to the role of MGAT5 and β1,6-GlcNAc branched N-glycans in cellular mechanisms that contribute to the development and progression of solid tumors. We also provide insight into possible future clinical implications, such as the use of MGAT5 as a prognostic biomarker.