Protein expression and fucosylated glycans of the serum haptoglobin-&amp;beta; subunit in hepatitis B virus-based liver diseases

Shu, Hong; Zhang, Shu; Kang, Xiaonan; Li, Shan; Qin, Xue; Sun, Changgang; Lu, Haojie; Liu, Yinkun

doi:10.1093/abbs/gmr038

Cited by 23 publications

(18 citation statements)

References 26 publications

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“…Changes in fucosylation can be observed in nearly all malignancies, such as breast (16), hCC (17), colon (18) and lung cancer (19). high incidence of sLex in ER-negative breast tumors coincided with high expression of glycosyltransferases FUT3, FUT4 and ST3GAL6 (20).…”

Section: Discussionmentioning

confidence: 99%

miR-493-5p attenuates the invasiveness and tumorigenicity in human breast cancer by targeting FUT4

et al. 2016

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Abstract. Breast cancer is a leading cause of cancer-related mortality among women. Altered fucosylation was found to be closely associated with tumorigenesis and metastasis of breast cancer. MicroRNAs (miRNAs) are important regulators of cell proliferation and metastasis, and aberrant miRNA expression has been observed in breast cancer. The present study aimed to evaluate the level of fucosyltransferase IV (FUT4) and miR-493-5p in breast cancer and investigate their relationship. In the present study, we demonstrated the differential expressional profiles of FUT4 and miR-493-5p in 29 clinical breast cancer tissues, matched adjacent tissue samples and two breast carcinoma cell lines (MCF-7 and MDA-MB-231). Briefly, altered expression levels of FUT4 modified the invasive activities and tumorigenicity of the MCF-7 and MDA-MB-231 cells. Further study demonstrated that miR-493-5p plays a role as a suppressor in breast cancer cell invasion and tumorigenicity. Moreover, the expression levels of miR-493-5p were inversely proportional to those of FUT4 both at the mRNA and protein levels. Luciferase reporter assays confirmed that miR-493-5p bound to the 3'-untranslated (3'-UTR) region of FUT4, and inhibited the expression of FUT4 in breast cancer cells. Taken together, our data suggest that FUT4 may have a potential role in the treatment of breast cancer, as well as miR-493-5p is a novel regulator of invasiveness and tumorigenicity of breast cancer cells through targeting FUT4. The miR-493-5p/FUT4 pathway has therapeutic potential in breast cancer. IntroductionBreast cancer is the most common invasive cancer and the second cause of cancer-related death in women (1,2). Each year more than a half a million new cases of breast cancer are diagnosed in the US and Europe (3), and in China. Breast cancer is a very heterogeneous disease. Some patients are cured by the surgical removal of the primary tumor while other patients suffer from metastasis and progression of the disease, despite adjuvant therapy. Therefore, it is essential to develop effective and safer therapeutic modalities against breast cancer.Glycosylation is one of the important steps of protein post-translational modifications, and ~50% of proteins are glycosylated (4). Protein glycosylation plays a role in a variety of cellular biological functions, such as cell-cell and cell-substrate adhesion, membrane organization, cell immunogenicity and protein targeting (5). Specific changes in the glycosylation patterns of cell surface glycoprotein have been shown to enhance the metastatic potential of tumor cells. Aberrant expression of fucosylated glycans has also been detected in various types of tumors.The fucosyltransferase (FUT) family is a group of fucosylation synthases that catalyze the transfer of L-fucose (Fuc) from an activated GDP-β-L-Fuc to various acceptor molecules such as N-acetyllactosamine. The transfer of Fuc residue from the donor substrate, GDP-Fuc, is catalyzed to the oligosaccharide acceptor in a1, a1, FUT4, FUT5, FUT6, FUT7, FUT9, FUT10 and FUT1...

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Section: Discussionmentioning

confidence: 99%

miR-493-5p attenuates the invasiveness and tumorigenicity in human breast cancer by targeting FUT4

et al. 2016

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“…Aberrant expression of fucosylated glycans has been detected in breast cancer, 33 HCC, 34 colon cancer 35 and lung cancer. 36 The biosynthetic pathway of fucosylated glycans highlights the importance of FUTs.…”

Section: Discussionmentioning

confidence: 99%

FUT family mediates the multidrug resistance of human hepatocellular carcinoma via the PI3K/Akt signaling pathway

et al. 2013

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The fucosyltransferase (FUT) family is the key enzymes in cell-surface antigen synthesis during various biological processes such as tumor multidrug resistance (MDR). The aim of this work was to analyze the alteration of FUTs involved in MDR in human hepatocellular carcinoma (HCC) cell lines. Using mass spectrometry (MS) analysis, the composition profiling of fucosylated N-glycans differed between drug-resistant BEL7402/5-FU (BEL/FU) cells and the sensitive line BEL7402. Further analysis of the expressional profiles of the FUT family in three pairs of parental and chemoresistant human HCC cell lines showed that FUT4, FUT6 and FUT8 were predominant expressed in MDR cell lines. The altered levels of FUT4, FUT6 and FUT8 were responsible for changed drug-resistant phenotypes of BEL7402 and BEL/FU cells both in vitro and in vivo. In addition, regulating FUT4, FUT6 or FUT8 expression markedly modulated the activity of the phosphoinositide 3 kinase (PI3K)/Akt signaling pathway and MDR-related protein 1 (MRP1) expression. Inhibition of the PI3K/Akt pathway by its specific inhibitor wortmannin, or by Akt small interfering RNA (siRNA), resulted in decreased MDR of BEL/FU cells, partly through the downregulation of MRP1. Taken together, our results suggest that FUT4-, FUT6- or FUT8-mediated MDR in human HCC is associated with the activation of the PI3K/Akt pathway and the expression of MRP1, but not of P-gp, indicating a possible novel mechanism by which the FUT family regulates MDR in human HCC.

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“…Increased fuco- sylation is one of the frequently observed alterations of Hp glycoforms in cancer diseases, including the progression of liver disease to HCC. Shu et al (41) reported increased Le(x)-type singly fucosylated glycoforms of Hp in liver cirrhosis compared with healthy individuals; these changes were not sufficient to distinguish cirrhosis from hepatocellular carcinoma. Nakano et al (7) reported that patients with pancreatic cancer have elevated expression of singly fucosylated Le(x) structures that distinguish pancreatic cancer from controls.…”

Section: Glycosylation Of Hp In Cancer Andmentioning

confidence: 99%

Site-specific Glycoforms of Haptoglobin in Liver Cirrhosis and Hepatocellular Carcinoma

Pompach

Brnakova

Šanda

et al. 2013

Molecular & Cellular Proteomics

109

176

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Haptoglobin is a liver-secreted glycoprotein with four Nglycosylation sites. Its glycosylation was reported to change in several cancer diseases, which prompted us to examine site-specific glycoforms of haptoglobin in liver cirrhosis and hepatocellular carcinoma. To this end, we have used two-dimensional separation composed of hydrophilic interaction and nano-reverse phase chromatography coupled to QTOF mass spectrometry of the enriched glycopeptides. Our results show increased fucosylation of haptoglobin in liver disease with up to six fucoses associated with specific glycoforms of one glycopeptide. Structural analysis using exoglycosidase treatment and MALDI-MS/MS of detached permethylated glycans led to the identification of Lewis Y-type structures observed particularly in the pooled hepatocellular carcinoma sample. To confirm the increase of the Lewis Y structures observed by LC-MS, we have used immunoaffinity detection with Lewis Y-specific antibodies.

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Protein expression and fucosylated glycans of the serum haptoglobin-β subunit in hepatitis B virus-based liver diseases

Cited by 23 publications

References 26 publications

miR-493-5p attenuates the invasiveness and tumorigenicity in human breast cancer by targeting FUT4

miR-493-5p attenuates the invasiveness and tumorigenicity in human breast cancer by targeting FUT4

FUT family mediates the multidrug resistance of human hepatocellular carcinoma via the PI3K/Akt signaling pathway

Site-specific Glycoforms of Haptoglobin in Liver Cirrhosis and Hepatocellular Carcinoma

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