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Abstract

Glycosylation is a very important posttranslational modification of many biologically relevant molecules. A change in the structure of glycans added to glycoproteins and glycolipids is a common feature of the change to malignancy. With the cloning of many of the glycosyltransferases and the identification of specific target molecules, it is now possible to define these changes at the molecular level and to dissect the mechanisms involved. Within the mammary gland, mucin-type O-linked glycosylation has been studied most extensively. In normal resting, pregnant and lactating breast, mucin O-glycans are largely extended (core 2 type) structures. In contrast, mucin O-glycans found in breast carcinomas are often truncated (core 1 type). One mechanism that is responsible for this increase in core 1 structures is a change in the expression of glycosyltransferases, particularly an increase in the expression of the sialyltransferase, ST3Gal-1. The loss, at least to some degree, of core 2 based glycans is a consistent feature of MUC1 mucin when it is expressed by mammary tumours as demonstrated by the unmasking of the SM3 epitope in greater than 90% of breast carcinomas.

Probing mucin-type O-linked glycosylation in living animals

“…Changes in glycoconjugate expression levels, or in the structures of their pendant glycans, are characteristic of many cancers and have been exploited in a clinical setting. For example, the membranebound mucin glycoprotein MUC1 is highly overexpressed on breast cancers and displays O-linked glycans that are truncated compared with MUC1 on healthy breast tissue (42,43). The mucin glycoprotein CA125 is found at elevated levels in the serum of ovarian cancer patients and also displays aberrant glycosylation (44,45).…”

A Novel Membrane-associated Glycovariant of BEHAB/Brevican Is Up-regulated during Rat Brain Development and in a Rat Model of Invasive Glioma

“…Reduced or truncated N-and O-glycosylation of membrane proteins has been observed in several cancers (36,37). Because oligosaccharides may be involved in the adhesive interactions between cells and the ECM, a lack of normal glycosylation could promote the invasive ability of cancer cells by disrupting their normal association with the surrounding ECM (38).…”

The ST6GalNAc-I Sialyltransferase Localizes throughout the Golgi and Is Responsible for the Synthesis of the Tumor-associated Sialyl-Tn O-Glycan in Human Breast Cancer

“…1), with shorter core 1-based O-glycans being more dominant in many breast cancers (6,11). RT-PCR analysis of STn-positive and -negative breast cancers showed that cDNAs coding for the core 1-synthesizing enzyme (Fig.…”