Glycosylation is an Androgen-Regulated Process Essential for Prostate Cancer Cell Viability: Beyond the Abstract

Glycosylation is the addition of sugar groups, known as glycans, to proteins and lipids and is an important post-translational modification (Figure 1). Aberrant glycosylation is a universal feature of cancer cells and changes in glycan composition can have key roles in all of the recognised hallmarks of cancer.

Emerging data highlights the frequency of a wide range of alterations to glycans in prostate cancer, but despite this the prostate cancer glycome remains relatively understudied. This study identifies glycosylation as a global target for androgen control in prostate cancer cells. Glycosylation has an important role in many biological processes in cancer including cell adhesion, migration, interactions with the cell matrix, immune surveillance, cell signalling and cellular metabolism. Our results suggest that alterations in patterns of glycosylation via androgen control might modify some, or all of these processes in prostate cancer.

Our study identifies a set of 31 glycosylation enzymes which are controlled by androgens in prostate cancer patients, and further defines a set of 8 enzymes (GALNT7, ST6GalNAc1, GCNT1, UAP1, PGM3, CSGALNACT1, ST6GAL1 and EDEM3), which are also significantly up-regulated in prostate cancer tissue and are essential for prostate cancer cell viability. These 8 glycosylation enzymes are linked to the synthesis of important cancer-associated glycans, including sialyl-Tn (sTn), sialyl LewisX (SLeX), O-GlcNAc and chondroitin sulphate. We show that synthesis of these glycans is also controlled by androgens in prostate cancer cells, highlighting an important link between androgens and the prostate cancer glycome.

Understanding glycan function and composition in the normal prostate and in prostate cancer will be vital to improve risk stratification and therapeutic strategies in patients with prostate cancer. Prostate cancer is characterised by prognostic heterogeneity and there is a key clinical need to develop biomarkers to help distinguish indolent from aggressive disease.  The prostate is an abundant secretor of glycoproteins of all types, and as such alterations to glycans and glycoproteins are attractive potential diagnostic targets. The most widely used serological biomarkers used in cancer diagnosis and monitoring are glycoproteins, and monitoring the glycan composition of specific glycoproteins can dramatically increase their specificity as biomarkers. Glycans likely play roles in all aspects of prostate cancer progression and are therefore also attractive targets for therapeutic intervention. An increased understanding of how glycosylation modulates the biological function of prostate cancer cells will allow the development of a relatively unexploited field of drugs based on inhibitors, glycan antagonists and glycan function modulators.

 

Figure 1. Representative mammalian N-linked and O-linked glycans attached to proteins on the cell surface. 



Written by: Jennifer Munkley*

*Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK


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