Expression of sialyl‐Tn, Tn and T antigens in primary liver cancer

Sasaki, Motoko; Yamato, Taro; Nakanuma, Yasuni

doi:10.1046/j.1440-1827.1999.00867.x

Cited by 27 publications

(11 citation statements)

References 29 publications

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“…The expression of Tn and sialyl-Tn antigens has been detected in human hepatocellular carcinoma (59,60). EGFR O-glycosylation was shown to be modified by GALNT10 with overexpression in HCC, and previous finding showed that EGFR O-glycosylation could be regulated by GALNT2 (22).…”

Section: Discussionmentioning

confidence: 89%

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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Section: Discussionmentioning

confidence: 89%

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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“…In colon and breast cancer, an increase in the expression of short O-glycans, such as Tn, sialyl Tn, T, and sialyl T, often alters the function of glycoproteins and their antigenic property, as well as the potential of cancer cells to invade and metastasize (32 carcinoma has been reported (34,35). However, glycogenes responsible for these O-glycans and their functions in hepatocellular carcinoma remain largely unknown.…”

Section: Discussionmentioning

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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“…In contrast, the presence of sialyl Tn in keratoacanthoma is associated with tumor regression (22). Several short O-glycans have also been detected in human HCC, but not in the normal liver, by monoclonal antibodies or lectins (23,24). However, the role of short O-glycans in HCC progression and prognosis remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Mucin Glycosylating Enzyme GALNT2 Regulates the Malignant Character of Hepatocellular Carcinoma by Modifying the EGF Receptor

Liu²,

Hu³

et al. 2011

Cancer Research

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Extracellular glycosylation is a critical determinant of malignant character. Here, we report that N-acetylgalactosaminyltransferase 2 (GALNT2), the enzyme that mediates the initial step of mucin type-O glycosylation, is a critical mediator of malignant character in hepatocellular carcinoma (HCC) that acts by modifying the activity of the epidermal growth factor receptor (EGFR). GALNT2 mRNA and protein were downregulated frequently in HCC tumors where these events were associated with vascular invasion and recurrence. Restoring GALNT2 expression in HCC cells suppressed EGF-induced cell growth, migration, and invasion in vitro and in vivo. Mechanistic investigations revealed that the status of the O-glycans attached to the EGFR was altered by GALNT2, changing EGFR responses after EGF binding. Inhibiting EGFR activity with erlotinib decreased the malignant characters caused by siRNA-mediated knockdown of GALNT2 in HCC cells, establishing the critical role of EGFR in mediating the effects of GALNT2 expression. Taken together, our results suggest that GALNT2 dysregulation contributes to the malignant behavior of HCC cells, and they provide novel insights into the significance of O-glycosylation in EGFR activity and HCC pathogenesis. Cancer Res; 71(23); 7270-9. Ó2011 AACR.

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Expression of sialyl‐Tn, Tn and T antigens in primary liver cancer

Cited by 27 publications

References 29 publications

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

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

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

Mucin Glycosylating Enzyme GALNT2 Regulates the Malignant Character of Hepatocellular Carcinoma by Modifying the EGF Receptor

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