Overexpression of fucosyltransferase IV in A431 cell line increases cell proliferation
ABSTRACT Fucosyltransferase IV is an essential enzyme that catalyzes the synthesis of fucosylated oligosaccharides by transferring GDP-fucose to the terminal N-acetylglucosamine with the alpha1,3-linkage. Lewis Y oligosaccharide has a terminal alpha1,3-linked fucose residue and elevation of Lewis Y level is seen in many epithelial cancers. The mechanism of Lewis Y elevation in neoplastic cells is still largely unknown. To study the impact of fucosyltransferase IV on Lewis Y expression and its role on neoplastic cell proliferation, a pEGFP-N1-FUT4 recombinant plasmid was developed and stably transfected into A431 cells. We found that fucosyltransferase IV overexpression promoted cell proliferation and increased the expression of proliferating cell nuclear antigen that correlated with Lewis Y augmentation. Cell cycle analysis demonstrated that fucosyltransferase IV overexpression facilitated cell cycle progression. In conclusion, fucosyltransferase IV overexpression augments Lewis Y expression to trigger neoplastic cell proliferation. These studies suggest that fucosyltransferase IV may serve as a potential therapeutic target for the treatment of Lewis Y-positive epithelial cancers.
- SourceAvailable from: Faisal Aziz
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- "LeY is carried by the glycoproteins and glycolipids on cell surface, catalyzed by FUT1 or FUT4. LeY is highly expressed in 60-90% of human epithelial-origin cancer , including breast, colon, lung, and gastric cancers  . COX-2 is highly expressed at the early stage of cancers, being responsible for most of the prostanoid production *Address correspondence to this author at the "
ABSTRACT: Monoclonal antibody-based treatments of cancer which serve as magic 'bullets' have been established as one of the most successful therapeutic strategies. A variety of antigens has been investigated as targets for the mAb therapy of gastric cancer, including the carbohydrate type 2 blood group antigen. LewisY (LeY) is overexpressed on tumor cells surface either as glycolipids or glycoproteins. LeY is difucosylated oligosaccharide with the chemical structure [Fucα1→2Galβ1→ 4(Fucα1→3) GlcNAcβ1→R], which is catalyzed by fucosyltransferases, such as FUT 1 (α1→2) and FUT 4 (α1→3). The role of LeY antigen in cancer treatment and prevention has been extensively studied. Moreover, the cyclooxygenase-2 (COX-2) is an early event protein, highly expressed in H. pylori-related gastric cancer. COX-2 may play a pivotal part in the maintenance of tumor viability, growth, and metastasis. The COX-2 is upregulated in a variety of cancers, including gastric cancer. However, its inhibition may prevent or reverse gastric carcinogenesis. H. pylori mediated alteration of COX-2 through MAPKs pathway is one of the mechanisms that is implicated in gastric cancer. We have found COX-2 and LeY to be correlative sources of specific gastric biomarkers in gastric cancer, which is upregulated in the gastric cancer through MAPKs pathway. In addition, the anti-LeY antibody significantly downregulated the COX-2 expression through MAPKs pathway, helpful to the treatment of gastric cancer. In this review, we summarize the therapeutic effect of anti-LeY antibody, including the crucial role of COX-2 and LeY antigen in gastric cancer and discuss the COX-2 inhibition by anti-LeY antibody through MAPKs pathway.Current drug targets 02/2014; · 3.60 Impact Factor
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- "FUT4 interfered plasmid (FUT4-siRNA) and FUT4 overexpression plasmid (FUT4-cDNA) were constructed as before (Yang et al., 2007; Zhang et al., 2008). Cells were seeded on to 6-well plates. "
ABSTRACT: Adhesion molecules expressed on the uterine endometrium are potential receptive markers in embryo implantation. RL95-2 and HEC-1A cell lines represent the high- and low-receptive endometrial epithelium respectively. LeY (Lewis Y) is a difucosylated oligosaccharide highly expressed in the endometrium of some species during implantation. α1, 3 fucosylation of LeY is catalysed by FUT4 (fucosyltransferase IV), the key synthesis enzyme for LeY. We investigated whether the difference in receptivity between the 2 cell lines was related to different expressions of LeY and FUT4. RL95-2 cells expressed a higher level of LeY and FUT4 than HEC-1A cells, as shown by immunofluorescent staining, RT-PCR (reverse transcription-PCR) or Western blotting. FUT4-siRNA (small interfering RNA) transfection down-regulated FUT4 and LeY in RL95-2 cells, and inhibited the adhesion of the embryonic cells (JAR) to RL95-2 cell monolayer. FUT4-cDNA, however, increased the expression of FUT4 and LeY in HEC-1A cells, and increased the adhesion of embryonic cells to HEC-1A cell monolayer. Alterations of LeY level by up- or down-regulation of FUT4 also mediated EGFR (epidermal growth factor receptor)/MAPK (mitogen-activated protein kinase) signalling pathway. To conclude, the expression of LeY and FUT4 correlates with endometrial receptivity, making them potential new markers for the evaluation of endometrial receptivity.Cell Biology International 12/2011; 36(5):469-74. DOI:10.1042/CBI20100644 · 1.64 Impact Factor
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- "Recent evidence further supported the idea that the enhanced expression of Lewis in cancer may stimulate tumor growth. While increasing FUT4 and FUT7 expression promoted neoplastic cell proliferation and hepatocellular carcinoma (HCC) cell growth in vitro, respectively, reducing FUT3/6 expression suppressed colon carcinoma cell proliferation   . However, the underlying mechanism of FUTs-regulated cell growth remains unclear. "
ABSTRACT: The α1,3/4-fucosyltransferases (FUT) subfamily are key enzymes in cell surface antigen synthesis during various biological processes. A novel role of FUTs in tumorigenesis has been discovered recently, however, the underlying mechanism remains largely unknown. Here, we characterized FUT6, a member of α1,3/4-FUT subfamily, in human hepatocellular carcinoma (HCC). In HCC tissues, the expression levels of FUT6 and its catalytic product SLe(x) were significantly up-regulated. Overexpression of FUT6 in HCC cells enhanced S-phase cell population, promoted cell growth and colony formation ability. Moreover, subcutaneously injection of FUT6-overexpressing cells in nude mice promoted cell growth in vivo. In addition, elevating FUT6 expression markedly induced intracellular Akt phosphorylation, and suppressed the expression of the cyclin-dependent kinases inhibitor p21. Bath application of the PI3K inhibitor blocked FUT6-induced Akt phosphorylation, p21 suppression and cell proliferation. Our results suggest that FUT6 plays an important role in HCC growth by regulating the PI3K/Akt signaling pathway.Biochemical and Biophysical Research Communications 12/2011; 417(1):311-7. DOI:10.1016/j.bbrc.2011.11.106 · 2.28 Impact Factor