Cell surface protein glycosylation in cancer

Abstract

Glycosylation of proteins is one of the most important PTMs, with more than half of all human proteins estimated to be glycosylated. It is widely known that aberrant glycosylation has been implicated in many different diseases due to changes associated with biological function and protein folding. In cancer, there is increasing evidence pertaining to the role of glycosylation in tumour formation and metastasis. Alterations in cell surface glycosylation, particularly terminal motifs, can promote invasive behaviour of tumour cells that ultimately lead to the progression of cancer. While a majority of studies have investigated protein glycosylation changes in cancer cell lines and tumour tissue for individual cancers, the review presented here represents a comprehensive, in-depth overview of literature on the structural changes of glycosylation and their associated synthetic enzymes in five different cancer types originating from the breast, colon, liver, skin and ovary. More importantly, this review focuses on key similarities and differences between these cancers that reflect the importance of structural changes of cell surface N- and O-glycans, such as sialylation, fucosylation, degree of branching and the expression of specific glycosyltransferases for each cancer. It is envisioned that the understanding of these biologically relevant glycan alterations on cellular proteins will facilitate the discovery of novel glycan-based biomarkers which could potentially serve as diagnostic and prognostic indicators of cancer.

A lectin-based approach to detecting carcinogenesis in breast tissue

“…Overexpression of sialyl Lewis A , sialyl Lewis X and TF antigen has also been reported in other types of cancer (26). Similarly, increased terminal sialylation and core fucosylation levels have been detected in several forms of cancer, including liver, colorectal and ovarian cancer (23).…”

Uncovering the Binding Specificities of Lectins with Cells for Precision Colorectal Cancer Diagnosis Based on Multimodal Imaging

“…Numerous cancers including CRC have been known to relate with structural abnormalities of N‐ and/or O‐linked glycoproteins 8, 9. Several glycoproteins are reported as candidate biomarkers for cancers, and a part of them have been approved for clinical diagnosis of cancers by the US Food and Drug Administration 10, 11.…”

Semi-quantitative Measurement of a Specific Glycoform Using a DNA-tagged Antibody and Lectin Affinity Chromatography for Glyco-biomarker Development *

“…Glycoproteins with a Specific Glycan Structure-Many lines of evidence indicate that a subtle change in protein-glycan structures is associated with biological functions and various diseases (1,14,18). Although protein glycan synthesis is a nontemplate process and thus the glycan structures are heterogeneous, it is still necessary to identify and quantify specific glycoforms.…”

“…However, cumulative lines of evidence indicate that aberrant glycosylation is associated with various diseases including cancer (1), either by influencing the functionality of proteins and cells or as nonfunctional participants (2)(3)(4). Causal roles of aberrant glycosylation have been widely investigated in the development and progression of diseases, and significant progress has been made in the realm of cancer research (5).…”

“…Alpha feto protein (AFP) 1 -L 3 , a fucoform of AFP that is retained by the Lens culinaris lectin (LCA), is an extensively proven disease biomarker (7). AFP is frequently overexpressed in hepatic carcinoma cells and thus exists at high concentrations in blood of patients with hepatocellular carcinoma (HCC) (8).…”