Abstract
The oligosaccharide chains, or glycans, that decorate cell surface glycoproteins and glycolipids are among the most complex and diverse structures in vertebrate cells. It is estimated the well over half of all human proteins are glycosylated. Their expression is exquisitely regulated and is the result of the coordinated activity of distinct glycosyltransferases and glycosyl hydrolases that add or remove individual sugars to complete each glycan chain. Aberrantly expressed cell surface glycoconjugates are associated with malignant transformation, tumor progression, and metastasis and are predominantly the result of alterations in their biosynthetic machinery. They mediate key pathophysiological events during tumorigenesis including altered cellular adhesion and invasivity, molecular trafficking, receptor activation, and intracellular signal transduction in tumors.
Highlights
This review focuses on the linkage between glycoconjugate structure/function and intracellular protein kinase activity modulation
These data suggest that glycoconjugate-mediated protein kinase/phosphatase activity modulation may help explain how altered glycogene expression can lead to enhanced metastasis and invasivity and provide a new approach for the creation of effective anti-cancer therapeutics
Fibroblast growth factor receptor (FGFR) forms a ternary complex at the cell surface with its ligand, FGF, and heparan sulfate proteoglycan which in turn leads to activation and phosphorylation of the receptor tyrosine kinase that triggers various intracellular signaling cascades, including the MAPK pathway [11,12,13,14].Lastly, the N-glycan β1,6GlcNAc branching associated with GnT-V activity can promote the cell motility through triggering Rho family signaling
Summary
This review focuses on the linkage between glycoconjugate structure/function and intracellular protein kinase activity modulation. These data suggest that glycoconjugate-mediated protein kinase/phosphatase activity modulation may help explain how altered glycogene expression can lead to enhanced metastasis and invasivity and provide a new approach for the creation of effective anti-cancer therapeutics.
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