The Impact of the Unfolded Protein Response and the Hexosamine Biosynthetic Pathway on Glycosylation

Abstract

Glycan changes, in addition to being traditional mediators of protein quality control, cell signaling, and metabolism, are intimately linked to the progression of cancer and can potentially act as novel therapeutic and diagnostic targets. Despite advances in our understanding that glycosylation plays a key role in protein folding, maturation, and function, there is only limited understanding of the interconnected nature of glycan alterations to endoplasmic reticulum stress, the unfolded protein response, and the development of cancer. This review aims to highlight the interdependence of these pathways and the way they feed into each other to maintain protein quality control, regulate key survival mechanisms, and promote cell viability.