<i>N</i>‐Acetylglucosaminyltransferase V as a possible aid for the evaluation of tumor invasiveness in patients with hepatocellular carcinoma

Yanagi, Masahiko; Aoyagi, Yoshinobu; Suda, Takafumi; Mita, Yuhsaku; Asakura, Hitoshi

doi:10.1046/j.1440-1746.2001.02612.x

Cited by 34 publications

(23 citation statements)

References 25 publications

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“…One well characterized example is that of increased activity of N-acetylglucosaminyltransferase V, a key enzyme in the formation of branching asparagine-linked oligosaccharides that has been linked to tumor invasion and metastasis in multiple cancers (25)(26)(27)(28). An increase of ␤-1,6-branched oligosaccharides within metastatic lymph nodes of breast carcinomas has been reported, and the presence of the branched oligosaccharides was associated with poor prognosis (28).…”

Section: Altered Glycoproteins and Cancermentioning

confidence: 99%

Lectin Capture Strategies Combined with Mass Spectrometry for the Discovery of Serum Glycoprotein Biomarkers

Drake

Schwegler

Malik

et al. 2006

Molecular & Cellular Proteomics

209

160

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The application of mass spectrometry to identify disease biomarkers in clinical fluids like serum using high throughput protein expression profiling continues to evolve as technology development, clinical study design, and bioinformatics improve. Previous protein expression profiling studies have offered needed insight into issues of technical reproducibility, instrument calibration, sample preparation, study design, and supervised bioinformatic data analysis. In this overview, new strategies to increase the utility of protein expression profiling for clinical biomarker assay development are discussed with an emphasis on utilizing differential lectin-based glycoprotein capture and targeted immunoassays. The carbohydrate binding specificities of different lectins offer a biological affinity approach that complements existing mass spectrometer capabilities and retains automated throughput options. Specific examples using serum samples from prostate cancer and hepatocellular carcinoma subjects are provided along with suggested experimental strategies for integration of lectin-based methods into clinical fluid expression profiling strategies. Our example workflow incorporates the necessity of early validation in biomarker discovery using an immunoaffinity-based targeted analytical approach that integrates well with upstream discovery technologies.

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Section: Altered Glycoproteins and Cancermentioning

confidence: 99%

Lectin Capture Strategies Combined with Mass Spectrometry for the Discovery of Serum Glycoprotein Biomarkers

Drake

Schwegler

Malik

et al. 2006

Molecular & Cellular Proteomics

209

160

View full text Add to dashboard Cite

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“…Accumulated evidence indicates that alterations in N-linked glycosylation are a hallmark of various liver diseases, including hepatocellular carcinoma (5,8). For instance, expression of N-acetylglucosaminyltransferase-III and -V is increased in hepatocellular carcinoma (9,10). An N-glycan profiling study identified novel N-glycan structures in serum as prognostic markers of hepatocellular carcinoma (11).…”

Section: Introductionmentioning

confidence: 99%

C1GALT1 Enhances Proliferation of Hepatocellular Carcinoma Cells via Modulating MET Glycosylation and Dimerization

Liu

Huang

et al. 2013

Cancer Research

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Altered glycosylation is a hallmark of cancer. The core 1 b1,3-galactosyltransferase (C1GALT1) controls the formation of mucin-type O-glycans, far overlooked and underestimated in cancer. Here, we report that C1GALT1 mRNA and protein are frequently overexpressed in hepatocellular carcinoma tumors compared with nontumor liver tissues, where it correlates with advanced tumor stage, metastasis, and poor survival. Enforced expression of C1GALT1 was sufficient to enhance cell proliferation, whereas RNA interferencemediated silencing of C1GALT1 was sufficient to suppress cell proliferation in vitro and in vivo. Notably, C1GALT1 attenuation also suppressed hepatocyte growth factor (HGF)-mediated phosphorylation of the MET kinase in hepatocellular carcinoma cells, whereas enforced expression of C1GALT1 enhanced MET phosphorylation. MET blockade with PHA665752 inhibited C1GALT1-enhanced cell viability. In support of these results, we found that the expression level of phospho-MET and C1GALT1 were associated in primary hepatocellular carcinoma tissues. Mechanistic investigations showed that MET was decorated with O-glycans, as revealed by binding to Vicia villosa agglutinin and peanut agglutinin. Moreover, C1GALT1 modified the O-glycosylation of MET, enhancing its HGF-induced dimerization and activation. Together, our results indicate that C1GALT1 overexpression in hepatocellular carcinoma activates HGF signaling via modulation of MET O-glycosylation and dimerization, providing new insights into how O-glycosylation drives hepatocellular carcinoma pathogenesis. Cancer Res; 73(17); 5580-90. Ó2013 AACR.

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“…nyltransferase-III and acetylglucosaminyltransferase-V in HCC were positively correlated with the malignant and metastatic potential of tumor cells (11)(12)(13). In addition, the ␣-1,6-fucosylation of ␣-fetoprotein provides a more accurate diagnosis of HCC from chronic liver disease and a good monitoring and prognosis marker for the early diagnosis of HCC (14).…”

mentioning

confidence: 97%

Decreased Expression of Hepatocyte Nuclear Factor 4α (Hnf4α)/MicroRNA-122 (miR-122) Axis in Hepatitis B Virus-associated Hepatocellular Carcinoma Enhances Potential Oncogenic GALNT10 Protein Activity

Liu

et al. 2015

Journal of Biological Chemistry

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Background: GALNT, the initial enzyme in mucin-type O-glycosylation, plays critical roles in cancer etiology. Results: GALNT10-induced cellular proliferation was associated with EGFR activation mediated by down-regulation of miR-122 in HBV-associated HCC. Conclusion: A regulatory pathway of Hnf4␣/miR-122/GALNT10/EGFR may represent a possible mechanism underlying HBV-associated hepatocarcinogenesis. Significance: This finding provides a novel role for O-glycosylation in HCC pathogenesis.

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N‐Acetylglucosaminyltransferase V as a possible aid for the evaluation of tumor invasiveness in patients with hepatocellular carcinoma

Abstract: The present study demonstrated that there was a close association between tumor invasiveness and GnT-V activity in sera, and that the measurement of GnT-V may improve prognostic estimates and therapeutic outcomes for patients with HCC.

Cited by 34 publications

References 25 publications

Lectin Capture Strategies Combined with Mass Spectrometry for the Discovery of Serum Glycoprotein Biomarkers

Lectin Capture Strategies Combined with Mass Spectrometry for the Discovery of Serum Glycoprotein Biomarkers

C1GALT1 Enhances Proliferation of Hepatocellular Carcinoma Cells via Modulating MET Glycosylation and Dimerization

Decreased Expression of Hepatocyte Nuclear Factor 4α (Hnf4α)/MicroRNA-122 (miR-122) Axis in Hepatitis B Virus-associated Hepatocellular Carcinoma Enhances Potential Oncogenic GALNT10 Protein Activity

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