Potential of N-glycan in cell adhesion and migration as either a positive or negative regulator

Gu, Jianguo; Taniguchi, Naoyuki

doi:10.4161/cam.2.4.6748

Cited by 76 publications

(55 citation statements)

References 27 publications

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“…Several research groups, including our lab, reported that alternations in the oligosaccharide portion of integrins, that are modulated by the expression of each glycosyltransferase gene such as GnT-III, GnT-V and α2,6 sialyltransferase (ST6GalI), regulate cell malignant phenotypes such as integrin-mediated cell migration and cell spreading [17]. Overexpression of GnT-V resulted in an increase in cell migration and invasion.…”

Section: N-glycans Regulate Integrin Functionsmentioning

confidence: 99%

Potential roles of N-glycosylation in cell adhesion

Isaji

et al. 2012

Glycoconj J

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131

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The functional units of cell adhesion are typically multiprotein complexes made up of three general classes of proteins; the adhesion receptors, the cell-extracellular matrix (ECM) proteins, and the cytoplasmic plaque/peripheral membrane proteins. The cell adhesion receptors are usually transmembrane glycoproteins (for example E-cadherin and integrin) that mediate binding at the extracellular surface and determine the specificity of cell-cell and cell-ECM recognition. E-cadherin-mediated cell-cell adhesion can be both temporally and spatially regulated during development, and represents a key step in the acquisition of the invasive phenotype for many tumors. On the other hand, integrin-mediated cell-ECM interactions play important roles in cytoskeleton organization and in the transduction of intracellular signals to regulate various processes such as proliferation, differentiation and cell migration. ECM proteins are typically large glycoproteins, including the collagens, fibronectins, laminins, and proteoglycans that assemble into fibrils or other complex macromolecular arrays. The most of these adhesive proteins are glycosylated. Here, we focus mainly on the modification of N-glycans of integrins and laminin-332, and a mutual regulation between cell adhesion and bisected N-glycan expression, to address the important roles of N-glycans in cell adhesion.

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Section: N-glycans Regulate Integrin Functionsmentioning

confidence: 99%

Potential roles of N-glycosylation in cell adhesion

Isaji

et al. 2012

Glycoconj J

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131

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“…An emerging area of interest is the importance of the carbohydrate structures in tumor cells, which have been linked to control of protein folding and stability, cell-cell recognition, adhesion, invasion, and metastatic potentials (6 -11). The post-translational enzymatic addition of glycans (glycosylation) to proteins is a potent modulator of the functions of many receptors involved in cell growth, adhesion, and signal transduction (11)(12)(13)(14) and is commonly seen in both in vitro and in vivo cancer models (15, 16). Furthermore, a growing body of studies has shown a clear correlation between aberrant glycosylation and human disease states, including cancers (11,17,18).…”

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confidence: 99%

Hypoxia-induced Changes to Integrin α 3 Glycosylation Facilitate Invasion in Epidermoid Carcinoma Cell Line A431

Ren

Hao

Law

et al. 2014

Molecular & Cellular Proteomics

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Hypoxia is a critical microenvironmental factor that drives cancer progression through angiogenesis and metastasis. Glycoproteins, especially those on the plasma membrane, orchestrate this process; however, questions remain regarding hypoxia-perturbed protein glycosylation in cancer cells. We focused on the effects of hypoxia on the integrin family of glycoproteins, which are central to the cellular processes of attachment and migration and have been linked with cancer in humans. We employed electrostatic repulsion hydrophilic interaction chromatography coupled with iTRAQ labeling and LC-MS/MS to identify and quantify glycoproteins expressed in A431. The results revealed that independent of the protein-level change, N-glycosylation modifications of integrin ␣ 3 (ITGA3) were inhibited by hypoxia, unlike in other integrin subunits. A combination of Western blot, flow cytometry, and cell staining assays showed that hypoxia-induced alterations to the glycosylation of ITGA3 prevented its efficient translocation to the plasma membrane. Mutagenesis studies demonstrated that simultaneous mutation of glycosites 6 and 7 of ITGA3 prevented its accumulation at the K562 cell surface, which blocked integrin ␣ 3 and ␤ 1 heterodimer formation and thus abolished ITGA3's interaction with extracellular ligands. By generating A431 cells stably expressing ITGA3 mutated at glycosites 6 and 7, we showed that lower levels of ITGA3 on the cell surface, as induced by hypoxia, conferred an increased invasive ability to cancer cells in vitro under hypoxic conditions. Taken together, these results revealed that ITGA3 translocation to the plasma membrane suppressed by hypoxia through inhibition of glycosylation facilitated cell invasion in A431. Molecular & Cellular Proteomics 13: 10.1074/mcp.M114.038505, 3126-3137, 2014.As solid tumors grow, those areas distant from the existing blood vessels can become chronically or intermittently deprived of sufficient oxygen. These hypoxic conditions place tremendous pressure on tumor cells and drive the development of increasingly malignant and metastatic phenotypes (1, 2). As metastases are responsible for more than 90% of human cancer-related deaths, much research has aimed to define the underlying molecular mechanisms of the tumor cell response to a hypoxic microenvironment (3-5). However, despite the evident clinical relevance of metastasis, the full complexity of the process remains incompletely understood. An emerging area of interest is the importance of the carbohydrate structures in tumor cells, which have been linked to control of protein folding and stability, cell-cell recognition, adhesion, invasion, and metastatic potentials (6 -11). The post-translational enzymatic addition of glycans (glycosylation) to proteins is a potent modulator of the functions of many receptors involved in cell growth, adhesion, and signal transduction (11)(12)(13)(14) and is commonly seen in both in vitro and in vivo cancer models (15, 16). Furthermore, a growing body of studies has shown a clear correlation betw...

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“…Approximately 50% of proteins in mammalian cells are modified with a variety of glycans, which are classified into two major groups, N-and O-glycans 5) . N-glycans are attached to certain asparagine residues of proteins with the Asn-X-Ser/Thr motif, whereas O-glycans are attached to a subset of serine and threonine residues 6) .…”

Section: N-glycosylationmentioning

confidence: 99%

“…2), and this leads to elongation of the polylactosamine structure, which controls the cell surface residency of receptors and is associated with some of the invasive characteristics of cancer cells 5,10,11) . The overexpression of GnT-V inhibits clustering of integrin α5β1, indicating that this mediates reduced adhesion and increased motility of cancer cells 12) .…”

Section: N-glycosylationmentioning

confidence: 99%

Effects of exercise on the hexosamine biosynthetic pathway and glycosylation

Shirato

Kizaki

Ohno

et al. 2012

JPFSM

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Minor amounts of glucose incorporated into the cells is metabolized via the hexosamine biosynthetic pathway, resulting in the production of uridine-5'-diphosphate-N-acetylglucosamine (UDP-GlcNAc), which is utilized as a donor substrate for the N-and O-linked glycosylation of extracellular and membrane proteins in the Golgi apparatus, or for the O-linked GlcNAc modification (O-GlcNAcylation) of intracellular proteins in the cytosol. In particular, O-GlcNAcylation, the addition of GlcNAc to serine/threonine residues, is reversibly regulated by the enzymatic activities of O-GlcNAc transferase (OGT) and O-GlcNAcase. Since OGT activity is sensitive to the intracellular UDP-GlcNAc level, flux via the hexosamine pathway influences O-GlcNAcylation. Actually, excess flux via the hexosamine pathway and resultant increased O-GlcNAcylation are associated with several pathophysiological conditions, including insulin resistance. To date, there are several studies addressing the effects of exercise on the hexosamine pathway and O-GlcNAcylation. Thus, this short review focuses on the relationships among exercise, the hexosamine pathway, O-GlcNAcylation, and insulin resistance.

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Potential of N-glycan in cell adhesion and migration as either a positive or negative regulator

Cited by 76 publications

References 27 publications

Potential roles of N-glycosylation in cell adhesion

Potential roles of N-glycosylation in cell adhesion

Hypoxia-induced Changes to Integrin α 3 Glycosylation Facilitate Invasion in Epidermoid Carcinoma Cell Line A431

Effects of exercise on the hexosamine biosynthetic pathway and glycosylation

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