Biosynthesis and Biological Significances of LacdiNAc Group on N- and O-Glycans in Human Cancer Cells.

Abstract

An increasing number of studies have shown that the disaccharide GalNAcβ1→4GlcNAc (LacdiNAc) group bound to N- and O-glycans in glycoproteins is expressed in a variety of mammalian cells. Biosynthesis of the LacdiNAc group was well studied, and two β4-N-acetylgalactosaminyltransferases, β4GalNAcT3 and β4GalNAcT4, have been shown to transfer N-acetylgalactosamine (GalNAc) to N-acetylglucosamine (GlcNAc) of N- and O-glycans in a β-1,4-linkage. The LacdiNAc group is often sialylated, sulfated, and/or fucosylated, and the LacdiNAc group, with or without these modifications, is recognized by receptors and lectins and is thus involved in the regulation of several biological phenomena, such as cell differentiation. The occurrences of the LacdiNAc group and the β4GalNAcTs appear to be tissue specific and are closely associated with the tumor progression or regression, indicating that they will be potent diagnostic markers of particular cancers, such as prostate cancer. It has been demonstrated that the expression of the LacdiNAc group on N-glycans of cell surface glycoproteins including β1-integrin is involved in the modulation of their protein functions, thus affecting cellular invasion and other malignant properties of cancer cells. The biological roles of the LacdiNAc group in cancer cells have not been fully understood. However, the re-expression of the LacdiNAc group on N-glycans, which is lost in breast cancer cells by transfection of the β4GalNAcT4 gene, brings about the partial restoration of normal properties and subsequent suppression of malignant phenotypes of the cells. Therefore, elucidation of the biological roles of the LacdiNAc group in glycoproteins will lead to the suppression of breast cancers.

• Authors: Kiyoko Hirano, Kiyoshi Furukawa
• Journal: Biomolecules (Biomolecules) Vol. 12 Issue 2 (01 24 2022) ISSN: 2218-273X [Electronic] Switzerland
• PMID: 35204696 (Publication Type: Journal Article, Review)

Chemical References

• Polysaccharides
• N-acetylgalactosaminyl-1-4-N-acetylglucosamine
• N-Acetylgalactosaminyltransferases
• Lactose

Topics

• Animals
• Breast Neoplasms
• Female
• Humans
• Lactose (analogs & derivatives, metabolism)
• Mammals (metabolism)
• N-Acetylgalactosaminyltransferases (metabolism)
• Polysaccharides (metabolism)