Physiological roles of N-acetylglucosaminyltransferase V (GnT-V) in mice

Miyoshi, Eiji; Terao, Mineko; Kamada, Y.

doi:10.5483/bmbrep.2012.45.10.190

Cited by 21 publications

(14 citation statements)

References 35 publications

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“…Although our results revealed that there were no significant differences between GnT-V expression and T or Clinical stages, it was reported that GnT-V expression is upregulated in the early stages of almost all cancers (Miyoshi et al 2012). However Multiple logistic regression analysis to determine the correlation between GnT-V expression and clinical and clinicopathological characteristics showed that the cases of negative GnT-V expression tended to be more invasive as determined by Anneroth grade.…”

Section: Discussioncontrasting

confidence: 85%

Negative expression of N-acetylglucosaminyltransferase V in oral squamous cell carcinoma correlates with poor prognosis

et al. 2013

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N-acetylglucosaminyltransferase V (GnT-V), an enzyme with a key role in the branching of asparagine-linked oligosaccharides, is strongly linked to tumor invasion and metastasis of many solid tumors. Here we searched for correlations between the clinical features of patients with oral squamous cell carcinoma (OSCC) and GnT-V expression in the tumor, and we studied the feasibility of using GnT-V as a marker for oral cancer prognosis. Samples from 68 patients with OSCC were examined by immunohistochemistry using antibodies against GnT-V. Correlations between the expression level of GnT-V in the tumor and patient clinical features were statistically analyzed. Positive GnT-V expression was found in 48 cases (70.6%), and negative GnT-V expression was found in 20 cases (29.4%). Negative GnT-V expression was associated with mode of invasion by multiple logistic regression analysis (OR: 3.605; P = 0.048). Biological characteristics of tumors and the Ki-67 labeling index were higher in tumors with negative GnT-V expression than in those with positive GnT-V expression, although the difference was not significant (P = 0.176). Patients with negative GnT-V expression had significantly shorter survival than those with tumors having positive GnT-V expression (5-year survival rate, 58.2% and 86.5%, respectively; P = 0.025). Negative GnT-V expression was a significant unfavorable prognostic factor for OSCC (hazard ratio, 4.246; P = 0.045). The loss of GnT-V expression is a likely indicator of tumors with high potential of tumor invasion and poor prognosis in OSCC patients.

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Section: Discussioncontrasting

confidence: 85%

Negative expression of N-acetylglucosaminyltransferase V in oral squamous cell carcinoma correlates with poor prognosis

et al. 2013

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“…Since our experiments point to CD147 and integrin-β1 as the major Gal-3 interacting proteins at the surface of dedifferentiated RPE cells, we next sought to investigate the state of N-glycosylation state of these proteins, because binding of Gal-3 critically depends on the presence of β-1,6-N-acetyl-D-glucosamine (GlcNAc) branched glycans [13]–[15]. In order to determine whether RPE-derived CD147 and integrin-β1 contain the respective N-glycosylation patterns, pull down experiments were conducted using agarose-bound plant lectins.…”

Section: Resultsmentioning

confidence: 99%

“…In this respect there is an increasing awareness in the literature that Gal-3 has a fine specificity for β-1,6-N-actyl-D-glucosamine (GlcNAc) branched glycans [13]–[15] and that sufficient Gal-3 binding to glycoproteins is critically dependent on the presence of specific oligosaccharides and complex glycan constellations in the vicinity of β-galactose (reviewed by Brewer) [16].Gal-3 has been found to associate with many cell surface molecules and the number of ligands identified is still likely to grow: these include carcinoembryonic antigen (CEA), MUC1, lysosomal-membrane-associated glycoproteins (LAMPs)-1 and -2, Mac-1 and Mac-3, CD98, CD45, CD71 [2], [17], [18], and the glycosylated transmembrane receptors for epidermal growth factor (EGF), transforming growth factor beta (TGF-β), or vascular endothelial growth factor (VEGF) [12], [14], among others. Although the functional relevance of these interactions is not known in all cases, it has been found that association of the cell surface glycoproteins CD45 and CD71 with Gal-3 triggers T-cell apoptosis [2].…”

Section: Introductionmentioning

confidence: 99%

Galectin-3 Induces Clustering of CD147 and Integrin-β1 Transmembrane Glycoprotein Receptors on the RPE Cell Surface

et al. 2013

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Proliferative vitreoretinopathy (PVR) is a blinding disease frequently occurring after retinal detachment surgery. Adhesion, migration and matrix remodeling of dedifferentiated retinal pigment epithelial (RPE) cells characterize the onset of the disease. Treatment options are still restrained and identification of factors responsible for the abnormal behavior of the RPE cells will facilitate the development of novel therapeutics. Galectin-3, a carbohydrate-binding protein, was previously found to inhibit attachment and spreading of retinal pigment epithelial cells, and thus bares the potential to counteract PVR-associated cellular events. However, the identities of the corresponding cell surface glycoprotein receptor proteins on RPE cells are not known. Here we characterize RPE-specific Gal-3 containing glycoprotein complexes using a proteomic approach. Integrin-β1, integrin-α3 and CD147/EMMPRIN, a transmembrane glycoprotein implicated in regulating matrix metalloproteinase induction, were identified as potential Gal-3 interactors on RPE cell surfaces. In reciprocal immunoprecipitation experiments we confirmed that Gal-3 associated with CD147 and integrin-β1, but not with integrin-α3. Additionally, association of Gal-3 with CD147 and integrin-β1 was observed in co-localization analyses, while integrin-α3 only partially co-localized with Gal-3. Blocking of CD147 and integrin-β1 on RPE cell surfaces inhibited binding of Gal-3, whereas blocking of integrin-α3 failed to do so, suggesting that integrin-α3 is rather an indirect interactor. Importantly, Gal-3 binding promoted pronounced clustering and co-localization of CD147 and integrin-β1, with only partial association of integrin-α3. Finally, we show that RPE derived CD147 and integrin-β1, but not integrin-α3, carry predominantly β-1,6-N-actyl-D-glucosamine-branched glycans, which are high-affinity ligands for Gal-3. We conclude from these data that extracellular Gal-3 triggers clustering of CD147 and integrin-β1 via interaction with β1,6-branched N-glycans on RPE cells and hypothesize that Gal-3 acts as a positive regulator for CD147/integrin-β1 clustering and therefore modifies RPE cell behavior contributing to the pathogenesis of PVR. Further investigations at this pathway may aid in the development of specific therapies for PVR.

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“…A previous study demonstrated that GnT-V is an important glycosyltransferase, which promotes this malignant transformation process by catalyzing the formation of β1,6-branched oligosaccharides (19). Furthermore, GnT-V is overexpressed in various malignant tumor types, thereby promoting the malignant transformation process (21,22). Therefore, it was hypothesized that reducing the expression of GnT-V may provide a suitable strategy for ameliorating the progression of certain tumor types.…”

Section: Discussionmentioning

confidence: 99%

Effect of GnT-V knockdown on the proliferation, migration and invasion of the SMMC7721/R human hepatocellular carcinoma drug-resistant cell line

Zhang

et al. 2015

Molecular Medicine Reports

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Hepatocellular carcinoma (HCC) is a commonly occurring malignant tumor, with a high incidence rate. The present study aimed to investigate the effect of knocking down the N‑glycosyltransferase‑V (GnT‑V) protein on the proliferation, migration and invasion of the human HCC drug‑resistant cell line, SMMC7721/R. SMMC7721/R cells with GnT‑V‑knockdown (SMMC‑7721/R‑GnT‑V) were constructed using the method of lentiviral transfection. The expression of GnT‑V was assessed using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting. Cell proliferation was determined using an MTT assay, and the extent of cellular apoptosis was assessed using flow cytometric analysis. Additionally, the metastatic ability of the cells in vitro was analyzed using cell adhesion and invasion assays. Western blotting was used to investigate the protein expression levels of caspase‑3, caspase‑9, Bcl‑2, Bax, matrix metalloproteinase (MMP)‑2 and MMP‑9, and RT‑qPCR was used to determine the mRNA expression levels of the genes for the breast cancer resistance protein and P‑glycoprotein in the SMMC‑7721/R cells. Taken together, the results of the present study revealed that the knockdown of GnT‑V significantly suppressed the proliferation, migration and invasion (P<0.05) of the SMMC‑7721/R cells. Furthermore, the possible mechanism underlying these phenomena may be associated with the induction of mitochondria‑mediated apoptosis, inhibition of the degradation of the extracellular matrix and an enhancement of the drug-sensitivity. GnT‑V‑knockdown may therefore be used to treat drug‑resistant HCC in the future.

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Physiological roles of N-acetylglucosaminyltransferase V (GnT-V) in mice

Cited by 21 publications

References 35 publications

Negative expression of N-acetylglucosaminyltransferase V in oral squamous cell carcinoma correlates with poor prognosis

Negative expression of N-acetylglucosaminyltransferase V in oral squamous cell carcinoma correlates with poor prognosis

Galectin-3 Induces Clustering of CD147 and Integrin-β1 Transmembrane Glycoprotein Receptors on the RPE Cell Surface

Effect of GnT-V knockdown on the proliferation, migration and invasion of the SMMC7721/R human hepatocellular carcinoma drug-resistant cell line

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