Mucin-Type O-Glycosylation in Gastric Carcinogenesis

Abstract

Mucin-type O-glycosylation plays a crucial role in several physiological and pathological processes of the gastric tissue. Modifications in enzymes responsible for key glycosylation steps and the consequent abnormal biosynthesis and expression of their glycan products constitute well-established molecular hallmarks of disease state. This review addresses the major role played by mucins and associated O-glycan structures in Helicobacter pylori adhesion to the gastric mucosa and the subsequent establishment of a chronic infection, with concomitant drastic alterations of the gastric epithelium glycophenotype. Furthermore, alterations of mucin expression pattern and glycan signatures occurring in preneoplastic lesions and in gastric carcinoma are also described, as well as their impact throughout the gastric carcinogenesis cascade and in cancer progression. Altogether, mucin-type O-glycosylation alterations may represent promising biomarkers with potential screening and prognostic applications, as well as predictors of cancer patients’ response to therapy.

Core 1–derived mucin-type O-glycosylation protects against spontaneous gastritis and gastric cancer

“…Aberrant expression of mucin-type O-glycosylation has been observed in gastric cancer progression (Barresi et al, 2001; Duarte et al, 2016; Heneghan et al, 1998; Lindén et al, 2008; Persson et al, 2017), but whether and how truncation of O-glycosylation contributes to the pathogenesis of this disease is unclear. In this study, we show that deletion of core 1–derived O-glycans leads to impaired gastric mucin function and results in spontaneous inflammation-associated gastritis and gastric cancer.…”

“…Therefore, it is likely the lack of complex O-glycosylation due to core 1 O-glycan loss is affecting events at the mucosal surface (where Muc5AC is expressed). Importantly, both glycan truncation and alterations such as αGlcNAc deficiency are reported in gastric cancer (David et al, 1992; Duarte et al, 2016; Li et al, 2018; Mereiter et al, 2018; Springer, 1984; Werther et al, 1994), highlighting the diverse means by which O-glycans and their alterations contribute to gastric homeostasis and disease.…”

Biologic roles of the ABH and Lewis histo‐blood group antigens part II: thrombosis, cardiovascular disease and metabolism

“…In this review, we have focused on just a few of the biologic and pathologic processes that appear to be influenced by the ABH and related carbohydrate histo‐blood group antigens. Many more areas are the subject of active investigation, for example the role of these and related carbohydrate structures in carcinogenesis . The application of some of the newer glycobiological strategies such as glycoengineered cell lines, glycomic and glycoproteomic approaches, glycan microarray analysis, and the use of synthetic glycolipids and recombinant versions of glycosylated proteins coupled with the development of effective animal models will undoubtedly bring new insights into the biological roles of these structures .…”

Different Glycoconjugate Content in Mucus Secreting Cells of the Rat Fundic Gastric Glands

“…The gastric mucosa expresses MUC1, a transmembrane mucin that can also be released from the cell surface, and two secreted mucins, MUC5AC and MUC6. SMCs express MUC5AC and MUC1, whereas MNCs express MUC6 and MUC1 (Carlstedt et al, ; De Bolós et al, ; Ho et al, ; López‐Ferrer et al, ; Duarte et al, ). Most of the oligosaccharides in mucins are attached by O‐links to the protein core (Brockhausen, ).…”

“…express MUC6 and MUC1 (Carlstedt et al, 1995;De Bolós et al, 1995;Ho et al, 1995;López-Ferrer et al, 2000;Duarte et al, 2016). Most of the oligosaccharides in mucins are attached by O-links to the protein core (Brockhausen, 1999 (Duarte et al, 2016). Mucins also include a small number of oligosaccharides N-linked to the protein core (Corfield et al, 2001), including high- Table 1.…”