Abstract
The Golgi enzyme beta1,6 N-acetylglucosaminyltransferase V (Mgat5) is up-regulated in carcinomas and promotes the substitution of N-glycan with poly N-acetyllactosamine, the preferred ligand for galectin-3 (Gal-3). Here, we report that expression of Mgat5 sensitized mouse cells to multiple cytokines. Gal-3 cross-linked Mgat5-modified N-glycans on epidermal growth factor and transforming growth factor-beta receptors at the cell surface and delayed their removal by constitutive endocytosis. Mgat5 expression in mammary carcinoma was rate limiting for cytokine signaling and consequently for epithelial-mesenchymal transition, cell motility, and tumor metastasis. Mgat5 also promoted cytokine-mediated leukocyte signaling, phagocytosis, and extravasation in vivo. Thus, conditional regulation of N-glycan processing drives synchronous modification of cytokine receptors, which balances their surface retention against loss via endocytosis.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Cell Line, Tumor
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Cell Membrane / metabolism
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Cell Movement
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Cell Transformation, Neoplastic
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Endocytosis*
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ErbB Receptors / metabolism*
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Galectin 3 / metabolism
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Genetic Vectors
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Glycosylation
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Golgi Apparatus / enzymology
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Growth Substances / metabolism
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Growth Substances / pharmacology
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Macrophages, Peritoneal / physiology
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Mammary Neoplasms, Animal / metabolism
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Mammary Neoplasms, Animal / pathology
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Mice
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Mice, Transgenic
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N-Acetylglucosaminyltransferases / genetics
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N-Acetylglucosaminyltransferases / metabolism*
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Neoplasm Metastasis
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Phagocytosis
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Polysaccharides / metabolism*
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Receptors, Cytokine / metabolism*
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Receptors, Transforming Growth Factor beta / metabolism*
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Signal Transduction
Substances
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Galectin 3
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Growth Substances
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Polysaccharides
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Receptors, Cytokine
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Receptors, Transforming Growth Factor beta
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poly-N-acetyllactosamine
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N-Acetylglucosaminyltransferases
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alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase
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ErbB Receptors