The bisecting GlcNAc in cell growth control and tumor progression

• Published in: Glycoconjugate journal Vol. 29; no. 8-9; pp. 609 - 618
• Main Authors: Miwa, Hazuki E., Song, Yinghui, Alvarez, Richard, Cummings, Richard D., Stanley, Pamela
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.12.2012; Springer Nature B.V
• Subjects: Acetylglucosamine - metabolism; Animals; Biochemistry; Biomedical and Life Sciences; Cell Proliferation; Disease Progression; Galectins - metabolism; Genetic engineering; Glycosylation; Humans; Intercellular Signaling Peptides and Proteins - metabolism; Life Sciences; N-Acetylglucosaminyltransferases - metabolism; Neoplasms - enzymology; Neoplasms - metabolism; Neoplasms - pathology; Pathology; Polypeptides; Signal Transduction; Tumors; Glycosylation; Bisecting GlcNAc; Galectins; Complex N-glycans; Mgat3
• ISSN: 0282-0080; 1573-4986; 1573-4986
• DOI: 10.1007/s10719-012-9373-6

The bisecting GlcNAc is transferred to the core mannose residue of complex or hybrid N-glycans on glycoproteins by the β1,4- N -acetylglucosaminyltransferase III (GlcNAcT-III) or MGAT3. The addition of the bisecting GlcNAc confers unique lectin recognition properties to N-glycans. Thus, LEC10 gain-of-function Chinese hamster ovary (CHO) cells selected for the acquisition of ricin resistance, carry N-glycans with a bisecting GlcNAc, which enhances the binding of the erythroagglutinin E-PHA, but reduces the binding of ricin and galectins-1, -3 and -8. The altered interaction with galactose-binding lectins suggests that the bisecting GlcNAc affects N-glycan conformation. LEC10 mutants expressing polyoma middle T antigen (PyMT) exhibit reduced growth factor signaling. Furthermore, PyMT-induced mammary tumors lacking MGAT3, progress more rapidly than tumors with the bisecting GlcNAc on N-glycans of cell surface glycoproteins. In recent years, evidence for a new paradigm of cell growth control has emerged involving regulation of cell surface residency of growth factor and cytokine receptors via interactions and cross-linking of their branched N-glycans with a lattice of galectin(s). Specific cross-linking of glycoprotein receptors in the lattice regulates their endocytosis, leading to effects on growth factor-induced signaling. This review will describe evidence that the bisecting GlcNAc of N-glycans regulates cellular signaling and tumor progression, apparently through modulating N-glycan/galectin interactions.