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sialyltransferase

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https://www.readbyqxmd.com/read/29233887/st6gal-i-sialyltransferase-promotes-tumor-necrosis-factor-tnf-mediated-cancer-cell-survival-via-sialylation-of-the-tnf-receptor-1-tnfr1-death-receptor
#1
Andrew T Holdbrooks, Colleen M Britain, Susan L Bellis
Activation of the TNFR1 death receptor by TNF induces either cell survival or cell death. However, the mechanisms mediating these distinct outcomes remain poorly understood. In the present study, we report that the ST6Gal-I sialyltransferase, an enzyme upregulated in numerous cancers, sialylates TNFR1, and thereby protects tumor cells from TNF-induced apoptosis. Using pancreatic and ovarian cancer cells with ST6Gal-I knockdown or overexpression, we determined that α2-6 sialylation of TNFR1 had no effect on early TNF-induced signaling events including the rapid activation of NFκB, JNK, ERK, and Akt (occurring within 15m)...
December 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29191829/st6gal-i-sialyltransferase-promotes-chemoresistance-in-pancreatic-ductal-adenocarcinoma-by-abrogating-gemcitabine-mediated-dna-damage
#2
Asmi Chakraborty, Kaitlyn A Dorsett, Hoa Q Trummell, Eddy S Yang, Patsy G Oliver, James A Bonner, Donald J Buchsbaum, Susan L Bellis
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor prognosis. Gemcitabine, as a single agent or in combination therapy, remains the frontline chemotherapy despite its limited efficacy due to de novo or acquired chemoresistance. There is an acute need to decipher mechanisms underlying chemoresistance and identify new targets to improve patient outcomes. Here we report a novel role for the ST6Gal-I sialyltransferase in gemcitabine resistance. Utilizing MiaPaCa-2 and BxPC-3 PDAC cells, we find that knockdown (KD) of ST6Gal-I expression, as well as removal of surface α2-6 sialic acids by neuraminidase, enhances gemcitabine-mediated cell death assessed via colonogenic assays and cleaved caspase 3 expression...
November 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29119617/computer-aided-design-of-human-sialyltransferase-inhibitors-of-hst8sia-iii
#3
Christopher Dobie, Andrew P Montgomery, Rémi Szabo, Danielle Skropeta, Haibo Yu
Sialyltransferase (ST) upregulation and the resultant hypersialylation of tumour cell surfaces is an established hallmark of many cancers including lung, breast, ovarian, pancreatic and prostate cancer. The role of ST enzymes in tumour cell growth and metastasis, as well as links to multi-drug resistance, has seen ST inhibition emerge as a target for potential antimetastatic cancer treatments. The most potent of these reported inhibitors are transition-state analogues. Although there are several examples of these in the literature, many have suspected poor pharmacokinetic properties and are not readily synthetically accessible...
November 9, 2017: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/29104485/cell-recognition-molecule-l1-regulates-cell-surface-glycosylation-to-modulate-cell-survival-and-migration
#4
Gang Shi, Yue Du, Yali Li, Yue An, Zhenwei He, Yingwei Lin, Rui Zhang, Xiaofei Yan, Jianfeng Zhao, Shihua Yang, Pang Nghee Kheem Brendan, Fang Liu
Background: Cell recognition molecule L1 (L1) plays an important role in cancer cell differentiation, proliferation, migration and survival, but its mechanism remains unclear. Methodology/Principal: Our previous study has demonstrated that L1 enhanced cell survival and migration in neural cells by regulating cell surface glycosylation. In the present study, we show that L1 affected cell migration and survival in CHO (Chinese hamster ovary) cell line by modulation of sialylation and fucosylation at the cell surface via the PI3K (phosphoinositide 3-kinase) and Erk (extracellularsignal-regulated kinase) signaling pathways...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29089525/transition-state-based-st6gal-i-inhibitors-mimicking-the-phosphodiester-linkage-with-a-triazole-or-carbamate-through-an-enthalpy-entropy-compensation
#5
Andrew P Montgomery, Danielle Skropeta, Haibo Yu
Human β-galactoside α-2,6-sialyltransferase I (ST6Gal I) catalyses the synthesis of sialylated glycoconjugates. Overexpression of ST6Gal I is observed in many cancers, where it promotes metastasis through altered cell surface sialylation. A wide range of sialyltransferase inhibitors have been developed, with analogues structurally similar to the transition state exhibiting the highest inhibitory activity. To improve synthetic accessibility and pharmacokinetics of previously reported inhibitors, the replacement of the charged phosphodiester linker with a potential neutral isostere such as a carbamate or a 1,2,3-triazole has been investigated...
October 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29076618/glycosylate-and-move-the-glycosyltransferase-maf-is-involved-in-bacterial-flagella-formation
#6
Gerlind Sulzenbacher, Véronique Roig-Zamboni, Régine Lebrun, Yann Guérardel, Dorothée Murat, Pascal Mansuelle, Nao Yamakawa, Xin-Xin Quian, Renaud Vincentelli, Yves Bourne, Long-Fei Wu, François Alberto
The flagella of various Gram-negative bacteria are decorated with diverse glycan structures, amongst them nonulosonic acids related to the sialic acid family. Although nonulosonic sugar biosynthesis pathways have been dissected in various pathogens, the enzymes transferring the sugars onto flagellin are still poorly characterized. The deletion of genes coding for Motility associated factors (Mafs) found in many pathogenic strains systematically gives rise to non-flagellated bacteria lacking specific nonulosonic sugars on the flagellins, therefore relating Maf function to flagellin glycosylation and bacterial motility...
October 27, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/29057592/the-role-of-sialic-acids-in-the-immune-recognition-of-xenografts
#7
REVIEW
Beth M French, Selin Sendil, Richard N Pierson, Agnes M Azimzadeh
Presentation of sialic acid (Sia) varies among different tissues and organs within each species, and between species. This diversity has biologically important consequences regarding the recognition of cells by "xeno" antibodies (Neu5Gc vs Neu5Ac). Sia also plays a central role in inflammation by influencing binding of the asialoglycoprotein receptor 1 (ASGR-1), Siglec-1 (Sialoadhesin), and cellular interactions mediated by the selectin, integrin, and galectin receptor families. This review will focus on what is known about basic Sia structure and function in association with xenotransplantation, how changes in sialylation may occur in this context (through desialylation or changes in sialyltransferases), and how this fundamental pathway modulates adhesive and cell activation pathways that appear to be particularly crucial to homeostasis and inflammation for xenografts...
October 22, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/29030743/mir-182-and-mir-135b-mediate-the-tumorigenesis-and-invasiveness-of-colorectal-cancer-cells-via-targeting-st6galnac2-and-pi3k-akt-pathway
#8
Li Jia, Shihua Luo, Xiang Ren, Yang Li, Jialei Hu, Bing Liu, Lifen Zhao, Yujia Shan, Huimin Zhou
BACKGROUND: Metastasis is a leading cause of cancer-related death including colorectal cancer (CRC). MicroRNAs are known to regulate cancer pathways and to be expressed aberrantly in cancer. Aberrant sialylation is closely associated with malignant phenotype of tumor cells, including invasiveness and metastasis. AIM: This study aimed to investigate the association of miR-182 and miR-135b with proliferation and invasion by targeting sialyltransferase ST6GALNAC2 in CRC cells and explore the potential molecular mechanism...
December 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28935102/biosynthesis-of-legionaminic-acid-and-its-incorporation-into-glycoconjugates
#9
Ian C Schoenhofen, N Martin Young, Michel Gilbert
Legionaminic acids are analogs of sialic acid that occur in cell surface glycoconjugates of several bacteria. Because legionaminic acids share the same stereochemistry as sialic acid but differ at C7 and C9, they are interesting analogs to probe the impact of varying exocyclic moieties (C7-C9) on biological activities such as susceptibilities to sialidases, interactions with Siglecs and immunogenicity. There are currently no reports on the bacterial enzymes that transfer legionaminic acids to these cell surface glycoconjugates, but some mammalian and bacterial sialyltransferases display donor promiscuity and can use CMP-Leg5,7Ac2 efficiently enough to transfer Leg5,7Ac2 to their natural acceptor glycans...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28926673/combinatorial-genome-and-protein-engineering-yields-monoclonal-antibodies-with-hypergalactosylation-from-cho-cells
#10
Cheng-Yu Chung, Qiong Wang, Shuang Yang, Sean A Ponce, Brian J Kirsch, Hui Zhang, Michael J Betenbaugh
One of the key quality attributes of monoclonal antibodies is the glycan pattern and distribution. Two terminal galactose residues typically represent a small fraction of the total glycans from antibodies. However, antibodies with defined glycosylation properties including enhanced galactosylation have been shown to exhibit altered properties for these important biomedical modalities. In this study, the disruption of two α-2,3 sialyltransferases (ST3GAL4 and ST3GAL6) from Chinese Hamster Ovary (CHO) cells was combined with protein engineering of the Fc region to generate an IgG containing 80% bigalactosylated and fucosylated (G2F) glycoforms...
December 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28925387/a-vital-sugar-code-for-ricin-toxicity
#11
Jasmin Taubenschmid, Johannes Stadlmann, Markus Jost, Tove Irene Klokk, Cory D Rillahan, Andreas Leibbrandt, Karl Mechtler, James C Paulson, Julian Jude, Johannes Zuber, Kirsten Sandvig, Ulrich Elling, Thorsten Marquardt, Christian Thiel, Christian Koerner, Josef M Penninger
Ricin is one of the most feared bioweapons in the world due to its extreme toxicity and easy access. Since no antidote exists, it is of paramount importance to identify the pathways underlying ricin toxicity. Here, we demonstrate that the Golgi GDP-fucose transporter Slc35c1 and fucosyltransferase Fut9 are key regulators of ricin toxicity. Genetic and pharmacological inhibition of fucosylation renders diverse cell types resistant to ricin via deregulated intracellular trafficking. Importantly, cells from a patient with SLC35C1 deficiency are also resistant to ricin...
November 2017: Cell Research
https://www.readbyqxmd.com/read/28903359/expression-of-sialyl-tn-sugar-antigen-in-bladder-cancer-cells-affects-response-to-bacillus-calmette-gu%C3%A3-rin-bcg-and-to-oxidative-damage
#12
Paulo F Severino, Mariana Silva, Mylene Carrascal, Nadia Malagolini, Mariella Chiricolo, Giulia Venturi, Annalisa Astolfi, Mariangela Catera, Paula A Videira, Fabio Dall'Olio
The sialyl-Tn (sTn) antigen is an O-linked carbohydrate chain aberrantly expressed in bladder cancer (BC), whose biosynthesis is mainly controlled by the sialyltransferase ST6GALNAC1. Treatment with Bacillus Calmette-Guérin (BCG) is the most effective adjuvant immunotherapy for superficial BC but one third of the patients fail to respond. A poorly understood correlation between the expression of sTn and BC patient's response to BCG was previously observed. By analyzing tumor tissues, we showed that patients with high ST6GALNAC1 and IL-6 mRNA expression were BCG responders...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28898525/analyses-of-n-linked-glycans-of-prp-sc-revealed-predominantly-2-6-linked-sialic-acid-residues
#13
Elizaveta Katorcha, Ilia V Baskakov
Mammalian prions (PrP(Sc) ) consist of misfolded, conformationally altered, self-replicating states of the sialoglycoprotein called prion protein or PrP(C) . Recent studies revealed that the sialylation status of PrP(Sc) plays a major role in evading innate immunity and infecting a host. Establishing the type of linkage by which sialic acid residues are attached to galactose is important, as it helps to identify the sialyltransferases responsible for sialylating PrP(C) and outline strategies for manipulating the sialyation status of PrP(Sc) ...
November 2017: FEBS Journal
https://www.readbyqxmd.com/read/28783175/contribution-of-vascular-endothelial-growth-factor-receptor-2-sialylation-to-the-process-of-angiogenesis
#14
P Chiodelli, S Rezzola, C Urbinati, F Federici Signori, E Monti, R Ronca, M Presta, M Rusnati
Vascular endothelial growth factor receptor-2 (VEGFR2) is the main pro-angiogenic receptor expressed by endothelial cells (ECs). Using surface plasmon resonance, immunoprecipitation, enzymatic digestion, immunofluorescence and cross-linking experiments with specific sugar-binding lectins, we demonstrated that VEGFR2 bears both α,1-fucose and α(2,6)-linked sialic acid (NeuAc). However, only the latter is required for VEGF binding to VEGFR2 and consequent VEGF-dependent VEGFR2 activation and motogenic response in ECs...
August 7, 2017: Oncogene
https://www.readbyqxmd.com/read/28764968/production-of-human-milk-oligosaccharides-by-enzymatic-and-whole-cell-microbial-biotransformations
#15
Georg A Sprenger, Florian Baumgärtner, Christoph Albermann
Human milk oligosaccharides (HMO) are almost unique constituents of breast milk and are not found in appreciable amounts in cow milk. Due to several positive aspects of HMO for the development, health, and wellbeing of infants, production of HMO would be desirable. As a result, scientists from different disciplines have developed methods for the preparation of single HMO compounds. Here, we review approaches to HMO preparation by (chemo-)enzymatic syntheses or by whole-cell biotransformation with recombinant bacterial cells...
July 29, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28717006/extrinsic-sialylation-is-dynamically-regulated-by-systemic-triggers-in-vivo
#16
COMPARATIVE STUDY
Charles T Manhardt, Patrick R Punch, Christopher W L Dougher, Joseph T Y Lau
Recent reports have documented that extracellular sialyltransferases can remodel both cell-surface and secreted glycans by a process other than the canonical cell-autonomous glycosylation that occurs within the intracellular secretory apparatus. Despite association of the abundance of these extracellular sialyltransferases, particularly ST6Gal-1, with disease states such as cancer and a variety of inflammatory conditions, the prevalence of this extrinsic glycosylation pathway in vivo remains unknown. Here we observed no significant extrinsic sialylation in resting mice, suggesting that extrinsic sialylation is not a constitutive process...
August 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28687873/%C3%AE-2-6-linked-sialic-acid-serves-as-a-high-affinity-receptor-for-cancer-oncolytic-virotherapy-with-newcastle-disease-virus
#17
Qian Li, Ding Wei, Fei Feng, Xi-Long Wang, Can Li, Zhi-Nan Chen, Huijie Bian
PURPOSE: Newcastle disease virus (NDV) has been applied to oncolytic virotherapy for decades due to its naturally oncolytic property. In spite of the substantiation of the sialic acid receptors of NDV on host cells, knowledge of preference of sialic acid linkage in viral attachment and oncolytic effect is lacking and imperative to be elucidated. METHODS: Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues were used to determine the affinity and the preference of sialic acid receptor...
November 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28681122/lewis-x-antigen-is-associated-to-head-and-neck-squamous-cell-carcinoma-survival
#18
Martín E Rabassa, Adrian Pereyra, Liliana Pereyra, Amada Segal-Eiras, Martín C Abba, Maria V Croce
Head and neck squamous cell carcinoma (HNSCC) is an aggressive disease with poor prognosis without appropriate prognostic markers. Previous research shows that Lewis antigens have been involved in carcinoma dissemination and patients´ survival. Fucosyl and sialyltransferases are the enzymes implicated in the Lewis antigens synthesis. The purpose of this study was to evaluate the prognostic utility of Lewis antigens in HNSCC. We conducted a prospective research including histological samples from 79 patients with primary HNSCC...
July 5, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28553930/%C3%AE-2-6-sialylation-mediates-hepatocellular-carcinoma-growth-in-vitro-and-in-vivo-by-targeting-the-wnt-%C3%AE-catenin-pathway
#19
Y Zhao, A Wei, H Zhang, X Chen, L Wang, H Zhang, X Yu, Q Yuan, J Zhang, S Wang
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...
May 29, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28550122/the-blood-borne-sialyltransferase-st6gal-1-is-a-negative-systemic-regulator-of-granulopoiesis
#20
Christopher W L Dougher, Alexander Buffone, Michael J Nemeth, Mehrab Nasirikenari, Eric E Irons, Paul N Bogner, Joseph T Y Lau
Responding to systemic demands in producing and replenishing end-effector blood cells is predicated on the appropriate delivery and interpretation of extrinsic signals to the HSPCs. The data presented herein implicate the systemic, extracellular form of the glycosyltransferase ST6Gal-1 in the regulation of late-stage neutrophil development. ST6Gal-1 is typically a membrane-bound enzyme sequestered within the intracellular secretory apparatus, but an extracellular form is released into the blood from the liver...
August 2017: Journal of Leukocyte Biology
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