Mucin glycoproteins in neoplasia

Abstract

Mucins are high molecular weight glycoproteins that are heavily glycosylated with many oligosaccharide side chains linked O-glycosidically to the protein backbone. With the recent application of molecular biological methods, the structures of apomucins and regulation of mucin genes are beginning to be understood. At least nine human mucin genes have been identified to date. Although a complete protein sequence is known for only three human mucins (MUC1, MUC2, and MUC7), common motifs have been identified in many mucins. The pattern of tissue and cell-specific expression of these mucin genes are emerging, suggesting a distinct role for each member of this diverse mucin gene family. In epithelial cancers, many of the phenotypic markers for pre-malignant and malignant cells have been found on the carbohydrate and peptide moieties of mucin glycoproteins. The expression of carbohydrate antigens appears to be due to modification of peripheral carbohydrate structures and the exposure of inner core region carbohydrates. The expression of some of the sialylated carbohydrate antigens appears to correlate with poor prognosis and increased metastatic potential in some cancers. The exposure of peptide backbone structures of mucin glycoproteins in malignancies appears to be due to abnormal glycosylation during biosynthesis. Dysregulation of tissue and cell-specific expression of mucin genes also occurs in epithelial cancers. At present, the role of mucin glycoproteins in various stages of epithelial cell carcinogenesis (including the preneoplastic state and metastasis), in cancer diagnosis and immunotherapy is under investigation.

The cell surface mucin MUC1 limits the severity of influenza A virus infection

“…O-linked sialylated glycans known as the sialyl Tn and sialyl T antigens {Neu5Ac(a2-6)GalNAc and Neu5Ac(a2-6)[Gal(b1-3)]GalNAc respectively}. Although these truncated glycans are only weakly expressed by healthy cells, 28 we proposed that the presence of a2,6-linked sialic acid could mimic the decoy behavior of healthy MUC1 towards IAV. Two of the sMUC1 peptides encompassed a single copy of the 20 amino-acid MUC1 extracellular tandem repeat sequence SAPDTRPAPG-STAPPAHGVT with a single glycosylated threonine residue ( Figure 5a, i and ii), while the other two glycopeptides encoded shorter sequences GSTAPPAHGVT and a glycosylated serine ( Figure 5a, iii and iv).…”

Cathelicidins in inflammation and tissue repair: Potential therapeutic applications for gastrointestinal disorders

“…Mucus hypersecretion is one of the major causes of inflammatory airway diseases like chronic bronchitis, asthma and cystic fibrosis [23] . On the contrary, marked reduction in the colonic mucus have also been reported in ulcerative colitis (UC) [24,25] . However, the mechanisms regulating these changes are still not understood.…”

Bile acid regulates MUC2 transcription in colon cancer cells via positive EGFR/PKC/Ras/ERK/CREB, PI3K/Akt/IκB/NF-κB and p38/MSK1/CREB pathways and negative JNK/c-Jun/AP-1 pathway

“…Mucins are heavily glycosylated high molecular weight glycoproteins which are broadly classified into two types; secretory or membrane associated (3)(4)(5). About 20 different mucin genes have been identified and many of these mucins are normally expressed in tissue-and cell type-specific manner (1,3,5,6).…”

“…Mucins are heavily glycosylated high molecular weight glycoproteins which are broadly classified into two types; secretory or membrane associated (3)(4)(5). About 20 different mucin genes have been identified and many of these mucins are normally expressed in tissue-and cell type-specific manner (1,3,5,6). The intestinal mucus layer consists mainly of MUC2, a major intestinal mucin, synthesized and secreted by goblet cells, providing an effective barrier against pathogens, toxins, dietary components and endogenous and exogenous stimuli, such as digestive enzymes, bile acids and non-steroidal anti-inflammatory drugs (2,(5)(6)(7).…”

“…The intestinal mucus layer consists mainly of MUC2, a major intestinal mucin, synthesized and secreted by goblet cells, providing an effective barrier against pathogens, toxins, dietary components and endogenous and exogenous stimuli, such as digestive enzymes, bile acids and non-steroidal anti-inflammatory drugs (2,(5)(6)(7). Quantitative and/or qualitative alterations in mucins have been reported in infection/inflammation and neoplasia (3)(4)(5). These changes occur due to altered regulation of expression of mucin core proteins and of glycosyltransferases that lead to altered glycosylation of mucin core proteins (3)(4)(5).…”