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Metabolomics and human breast milkA unique and inimitable food for infants
Published in Moshe Hod, Vincenzo Berghella, Mary E. D'Alton, Gian Carlo Di Renzo, Eduard Gratacós, Vassilios Fanos, New Technologies and Perinatal Medicine, 2019
Flamina Cesare Marincola, Sara Corbu, Roberta Pintus, Angelica Dessì, Vassilios Fanos
Among the applications of metabolomics on HBM, particular attention has been addressed to human milk oligosaccharides (HMOs), the third most abundant component after lactose and fat. HMOs have been shown to play an important role in an infant's development, by influencing the composition of the gut microbiome, modulating the immune system, and helping protect against pathogens (25,26). The utilization of HMOs by the microbiome in the gut has been recently reviewed (27). Every lactating woman has a unique pattern of oligosaccharides. Their presence in HBM is influenced by maternal genetic factors (secretor status and Lewis blood epitopes) and, in particular it depends on the activity of specific fucosyltransferases (28): fucosyltransferase 2 (FUT2) catalyzes the addition of fucose residues via 1–2 linkages on Lewis blood group; fucosyltransferase 3 (FUT3) catalyzes the addition of fucose residues via an 1–3/4 linkage. Depending on the expression of active FUT2 and FUT3 enzymes, women phenotypes can be separated into four groups: (1) Lewis-positive secretors (Se+/Le+) with FUT3 and FUT2 active; (2) Lewis-positive nonsecretor (Se−/Le+) with FUT3 active and FUT2 inactive; (3) i.e., Lewis-negative secretors (Se+/Le−) with FUT3 inactive and FUT2 active; and (4) Lewis-negative nonsecretors (Se−/Le−) with FUT2 and FUT3 inactive.
Glycans: potential therapeutic targets for cholangiocarcinoma and their therapeutic and diagnostic implications
Published in Expert Opinion on Therapeutic Targets, 2021
Peripheral glycans, including fucosylated- and sialylated-glycans, were also demonstrated to promote the progression of CCA. Fucosylated-glycans, such as a(1,2)-fucose-modified glycan and Lewis-associated glycans were found to facilitate the migration and invasion of CCA cells [7–9]. Fucosyltransferase (FUT)-1, an enzyme response for a(1,2)-fucose modification, was found to regulate the EGF/EGFR activation in CCA cells [9]. Metastatic abilities of CCA cells were significantly suppressed by specific siRNA against FUT1 and FUT3. Neutralization of surface Lewis-associated antigens using a specific monoclonal antibodies against CA-S27 or sialyl-Lewis A (sLeA) could significantly reduce the metastatic abilities of CCA cells. The metastatic suppression effect was also observed after treatment with Ulex europaeus agglutinin-I (UEA-I, a(1,2)-fucose binding lectin).
Aberrant fucosylation enables breast cancer clusterin to interact with dendritic cell-specific ICAM-grabbing non-integrin (DC-SIGN)
Published in OncoImmunology, 2019
Antonela Merlotti, Alvaro López Malizia, Paula Michea, Pierre-Emmanuel Bonte, Christel Goudot, María Sol Carregal, Nicolás Nuñez, Christine Sedlik, Ana Ceballos, Vassili Soumelis, Sebastián Amigorena, Jorge Geffner, Eliane Piaggio, Juan Sabatte
The synthesis of fucosylated Lewis type motifs is regulated by the action of different fucosyltransferases (FUTs) in the Golgy complex. To study the expression of fucosyltransferases and clusterin we analyze a cohort of breast cancer patients previously caracherized by Chung et al, using single cell transcriptomics.24 This study provides the transcriptome analysis of 515 single cells from tumor samples of 11 patients with different breast cancer subtypes. Unsupervised principal component analysis (PCA) shows extensive intratumoral heterogeneity (Figure 3(a)). In Figure 3(b,c), tumor and different lineages of non-tumor cells where identified using gene expression signatures previously described.24 As shown on Figure 3(d,e), clusterin is predominantly expressed by tumor and stromal cells, but not by tumor infiltrating immune cells. We then analyzed the expression of FUTs that might be involved in clusterin fucosylation. The expression of different FUTs in breast cancer has already been reported.25–27 The expression of FUT1, FUT2 and FUT3 was detected in tumor cells while FUT11 expression was observed in tumor and non-tumor cells. As shown in Figure 3(f), clusterin and FUTs are coexpressed in a proportion of the cells. These cells are potential sources of fucosylated clusterin in breast cancer tissues.
Glycosylation and its implications in breast cancer
Published in Expert Review of Proteomics, 2019
Danielle A. Scott, Richard R. Drake
Fucosyltransferases catalyze the addition of fucose moieties to either terminal ends of the glycan structure in N-linked and O-linked structures, or to the core N-acetylglucosamine residues attached to asparagine in N-linked glycoproteins. Structurally, there are two main differences between fucose and other six-carbon sugars: a lack of a hydroxyl group on the C-6 carbon, and an L-configuration. Fucosyltransferases (FUT) are the enzymes responsible for adding fucose residues onto oligosaccharides. This reaction requires that substrate GDP-fucose, which can be synthesized from either that GDP-mannose-dependent de novo pathway or the free fucose-dependent salvage pathway in mammalian cells [126]. Fucose residues can be attached via α1,2-, α1,3-, or α1,4- linkages for outer arm modifications, or α1,6- for core fucosylation linkages. FUT1 or FUT2 are responsible for α1,2-linkages, and FUT3 or FUT4 are responsible for α1,4-linkages. α1,3-linkages can be formed from either FUT3, FUT4, FUT6, FUT7, FUT9, FUT10 or FUT11. Finally, core fucose modifications are facilitated by FUT8. There are no differences in masses for these fucose linkages, despite the fact that each are responsible for the synthesis of different antigens [80,126].