N-Glycans in cancer progression.

Abstract

N-Glycan branching in the medial-Golgi generates ligands for lattice-forming lectins (e.g., galectins) that regulate surface levels of glycoproteins including epidermal growth factor (EGF) and transforming growth factor-beta (TGF-beta) receptors. Moreover, functional classes of glycoproteins differ in N-glycan multiplicities (number of N-glycans/peptide), a genetically encoded feature of glycoproteins that interacts with metabolic flux (UDP-GlcNAc) and N-glycan branching to differentially regulate surface levels. Oncogenesis increases beta1,6-N-acetylglucosaminyltransferase V (encoded by Mgat5) expression, and its high-affinity galectin ligands promote surface retention of growth receptors with a reduced dependence on UDP-GlcNAc. Mgat5(-/-) tumor cells are less metastatic in vivo and less responsive to cytokines in vitro, but undergo secondary changes that support tumor cell proliferation. These include loss of Caveolin-1, a negative regulator of EGF signaling, and increased reactive oxygen species, an inhibitor of phosphotyrosine phosphatases. These studies suggest a systems approach to cancer treatment where the surface distribution of receptors is targeted through metabolism and N-glycan branching to induce growth arrest.

• Authors: Ken S Lau, James W Dennis
• Journal: Glycobiology (Glycobiology) Vol. 18 Issue 10 Pg. 750-60 (Oct 2008) ISSN: 1460-2423 [Electronic] England
• PMID: 18701722 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Polysaccharides
• N-Acetylglucosaminyltransferases

Topics

• Animals
• Disease Progression
• Humans
• N-Acetylglucosaminyltransferases (metabolism)
• Neoplasms (metabolism, pathology)
• Polysaccharides (metabolism)
• Protein Binding
• Signal Transduction