α2,6-linked sialic acids on N-glycans modulate the adhesion of hepatocarcinoma cells to lymph nodes

Wang, Shujing; Chen, Xixi; Wei, Anwen; Yu, Xiao; Niang, Bachir; Zhang, Jianing

doi:10.1007/s13277-014-2638-x

Cited by 30 publications

(13 citation statements)

References 30 publications

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“…16 To inhibit ST6Gal-I expression, MHCC97-H cells were transfected with shRNA sequences targeting ST6Gal-I and a negative control vector (shNC) was constructed as described previously. 16, 24 These cells were transfected with a mixture of plasmids and Lipofectamine 2000 (Invitrogen, Carlsbad, CA, USA) depending on the manufacturer’s instructions. To select stably transfected cells, the culture medium was replaced with complete medium containing 800 mg/ml of G418 (Sigma-Aldrich, Darmstadt, Germany) after 48 h. Modified expression was confirmed by qPCR and western blotting.…”

Section: Methodsmentioning

confidence: 99%

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RETRACTED ARTICLE: α2,6-Sialylation mediates hepatocellular carcinoma growth in vitro and in vivo by targeting the Wnt/β-catenin pathway

et al. 2017

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Abnormal sialylation due to overexpression of sialyltransferases has been associated with tumorigenesis and tumor progression. Although ST6Gal-I influences cancer persistence and progression by affecting various receptors, the underlying mechanisms and mediators remain largely obscure, especially in hepatocellular carcinoma (HCC). We found that ST6Gal-I expression was markedly upregulated in HCC tissues and cells, high levels being associated with aggressive phenotype and poor prognosis. Furthermore, we examined the roles and mechanisms of ST6Gal-I in HCC tumorigenesis and metastasis in vitro and in vivo. ST6Gal-I overexpression promoted proliferation, migration and invasion of Huh-7 cells, whereas its knockdown restricted these abilities in MHCC97-H cells. Additionally, in a mouse xenograft model, ST6Gal-I-knockdown MHCC97-H cells formed significantly smaller tumors, implying that ST6Gal-I overexpression can induce HCC cell malignant transformation. Importantly, enhanced HCC tumorigenesis and metastasis by ST6Gal-I may be associated with Wnt/β-catenin signaling promotion, including β-catenin nuclear transition and upregulation of downstream molecules. Together, our results suggest a role for ST6Gal-I in promoting the growth and invasion of HCC cells through the modulation of Wnt/β-catenin signaling molecules, and that ST6Gal-I might be a promising marker for prognosis and therapy of HCC.

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Section: Methodsmentioning

confidence: 99%

“…22, 23 In our previous study, we found that upregulation of ST6Gal-I increased the adhesive capability of mouse hepatocarcinoma cell to lymph node. 24 However, the predictive and prognostic values of ST6Gal-I and its effect on HCC progression remained unclear.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: α2,6-Sialylation mediates hepatocellular carcinoma growth in vitro and in vivo by targeting the Wnt/β-catenin pathway

et al. 2017

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“…ST6Gal-I is known to be highly expressed in multiple types of cancer, including colorectal, ovarian, oral, breast, epithelial and liver carcinomas [6–11], and its expression has been positively correlated with adhesion, invasion and metastasis in tumor cells [12–14]. Recently it has been reported that ST6Gal-I mediates the sialylation of tumor-necrosis factor receptor-1 (TNFR1) and Fas receptors to inhibit cell apoptosis, and plays a vital role in resistance to cisplatin-induced apoptosis of ovarian cancer [15, 16, 7].…”

Section: Introductionmentioning

confidence: 99%

ST6Gal-I modulates docetaxel sensitivity in human hepatocarcinoma cells via the p38 MAPK/caspase pathway

et al. 2016

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The β-galactoside α2-6-sialyltransferase 1 (ST6Gal-I) is the principal sialyltransferase responsible for the addition of α2-6-sialic acid to the termini N-glycans on cell surface. Although ST6Gal-I in cancer cell resistance to chemotherapeutics agents has been previously reported, the role of ST6Gal-I in clinical drug resistance of hepatocellular carcinoma (HCC) is not fully understood. In this study, we found that knockdown of ST6Gal-I increased the sensitivity of hepatocarcinoma MHCC97-H cells to docetaxel treatment by instigating the process of apoptosis. Silencing ST6Gal-I expression decreased the survival rate of MHCC97-H cells after docetaxel treatment. Importantly, ST6Gal-I silencing resulted in an increasing of phospho-p38, Bax, Bad, cytochrome c and the cleaved caspase-9, 3 and PARP, while a decreasing of the anti-apoptotic protein Bcl-2. In addition, we found that p38 MAPK and caspase-3 inhibitors can reduce the enhanced apoptosis levels of MHCC97-H cells resulted by either ST6Gal-I silencing or docetaxel treatment. Conversely, exogenous expression of ST6Gal-I in hepatocarcinoma Huh7 cells inhibited apoptotic cell death and prevented docetaxel-induced apoptosis by inhibiting p38 MAPK mediated mitochondrial-dependent pathway. Taken together, these results indicate that ST6Gal-I might play a positive role in mediating the survival of human hepatocarcinoma cells and could be a potential target for gene and antitumor drugs therapy.

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“…Previous studies have devoted much attention to the biological functions of protein α-2, 6-sialylation, but the regulatory mechanisms controlling sialylation levels are poorly understood2122. Eukaryotic cells need to maintain a sialylation steady state, because hypersialylation may result in cell dysfunction.…”

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confidence: 99%

TNF-α regulates the proteolytic degradation of ST6Gal-1 and endothelial cell-cell junctions through upregulating expression of BACE1

Deng

Zhang

Liu

et al. 2017

Sci Rep

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Endothelial dysfunction and monocyte adhesion to vascular endothelial cells are two critical steps in atherosclerosis development, and emerging evidence suggests that protein sialylation is involved in these processes. However, the mechanism underlying this phenomenon remains incompletely elucidated. In this study, we demonstrated that treatment with the proinflammatory cytokine TNF-α disrupted vascular endothelial cell-cell tight junctions and promoted monocyte endothelial cell adhesion. Western blotting and Sambucus nigra lectin (SNA) blotting analyses revealed that TNF-α treatment decreased α-2, 6-sialic acid transferase 1 (ST6Gal-I) levels and downregulated VE-Cadherin α-2, 6 sialylation. Further analysis demonstrated that TNF-α treatment upregulated β-site amyloid precursor protein enzyme 1 (BACE1) expression, thus resulting in sequential ST6Gal-I proteolytic degradation. Furthermore, our results revealed that PKC signaling cascades were involved in TNF-α-induced BACE1 upregulation. Together, these results indicated that the proinflammatory cytokine TNF-α impairs endothelial tight junctions and promotes monocyte-endothelial cell adhesion by upregulating BACE1 expression through activating PKC signaling and sequentially cleaving ST6Gal-I. Thus, inhibition of BACE1 expression may be a new approach for treating atherosclerosis.

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α2,6-linked sialic acids on N-glycans modulate the adhesion of hepatocarcinoma cells to lymph nodes

Cited by 30 publications

References 30 publications

RETRACTED ARTICLE: α2,6-Sialylation mediates hepatocellular carcinoma growth in vitro and in vivo by targeting the Wnt/β-catenin pathway

RETRACTED ARTICLE: α2,6-Sialylation mediates hepatocellular carcinoma growth in vitro and in vivo by targeting the Wnt/β-catenin pathway

ST6Gal-I modulates docetaxel sensitivity in human hepatocarcinoma cells via the p38 MAPK/caspase pathway

TNF-α regulates the proteolytic degradation of ST6Gal-1 and endothelial cell-cell junctions through upregulating expression of BACE1

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