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sialyltransferase

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https://www.readbyqxmd.com/read/29454317/oxidative-damage-and-response-to-bacillus-calmette-gu%C3%A3-rin-in-bladder-cancer-cells-expressing-sialyltransferase-st3gal1
#1
Paulo F Severino, Mariana Silva, Mylene Carrascal, Nadia Malagolini, Mariella Chiricolo, Giulia Venturi, Roberto Barbaro Forleo, Annalisa Astolfi, Mariangela Catera, Paula A Videira, Fabio Dall'Olio
BACKGROUND: Treatment with Bacillus Calmette-Guérin (BCG) is the gold standard adjuvant immunotherapy of non-muscle invasive bladder cancer (NMIBC), although it fails in one third of the patients. NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown. METHODS: The human bladder cancer (BC) cell line HT1376 strongly expressing the T antigen, was retrovirally transduced with the ST3GAL1 cDNA or with an empty vector, yielding the cell lines HT1376sT and HT1376T , that express, respectively, either the sT or the T antigens...
February 17, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29440651/reconstruction-of-the-sialylation-pathway-in-the-ancestor-of-eukaryotes
#2
Daniel Petit, Elin Teppa, Ugo Cenci, Steven Ball, Anne Harduin-Lepers
The biosynthesis of sialylated molecules of crucial relevance for eukaryotic cell life is achieved by sialyltransferases (ST) of the CAZy family GT29. These enzymes are widespread in the Deuterostoma lineages and more rarely described in Protostoma, Viridiplantae and various protist lineages raising the question of their presence in the Last eukaryotes Common Ancestor (LECA). If so, it is expected that the main enzymes associated with sialic acids metabolism are also present in protists. We conducted phylogenomic and protein sequence analyses to gain insights into the origin and ancient evolution of ST and sialic acid pathway in eukaryotes, Bacteria and Archaea...
February 13, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29439861/enhancement-of-glycosylation-by-stable-co-expression-of-two-sialylation-related-enzymes-on-chinese-hamster-ovary-cells
#3
Nguyen Thi Sam, Ryo Misaki, Takao Ohashi, Kazuhito Fujiyama
Sialic acid plays important roles in stabilization and modulation of the interaction of molecules and membranes in organisms. Due to its high electronegativity, sialic acid can promote binding effects of molecules and support the transportation of drugs and ions in cells. This also strengthens cells against degradation from glycosidases and proteases. Hence sialic acid helps glycoproteins extend their half-lives and bioactivity. On the other hand, Chinese hamster ovary (CHO) cells have been widely used as a workhorse in biopharmaceutical fields in part due to the similarity between their glycan properties and those in humans...
February 10, 2018: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/29434218/association-of-cytosolic-sialidase-neu2-with-plasma-membrane-enhances-fas-mediated-apoptosis-by-impairing-pi3k-akt-mtor-mediated-pathway-in-pancreatic-cancer-cells
#4
Shalini Nath, Chhabinath Mandal, Uttara Chatterjee, Chitra Mandal
Modulation of sialylation by sialyltransferases and sialidases plays essential role in carcinogenesis. There are few reports on sialyltransferase, however, the contribution of cytosolic sialidase (Neu2) remains unexplored in pancreatic ductal adenocarcinoma (PDAC). We observed lower expression of Neu2 in different PDAC cells, patient tissues, and a significant strong association with clinicopathological characteristics. Neu2 overexpression guided drug-resistant MIAPaCa2 and AsPC1 cells toward apoptosis as evidenced by decreased Bcl2/Bax ratio, activation of caspase-3/caspase-6/caspase-8, PARP reduction, reduced CDK2/CDK4/CDK6, and cyclin-B1/cyclin-E with unaffected caspase-9...
February 12, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29433940/n-glycan-sialylation-in-a-silkworm-baculovirus-expression-system
#5
Masatoshi Suganuma, Tsuyoshi Nomura, Yukiko Higa, Yukiko Kataoka, Shunsuke Funaguma, Hironobu Okazaki, Takeo Suzuki, Kazuhito Fujiyama, Hideki Sezutsu, Ken-Ichiro Tatematsu, Toshiki Tamura
A silkworm-baculovirus system is particularly effective for producing recombinant proteins, including glycoproteins. However, N-glycan structures in silkworm differ from those in mammals. Glycoproteins in silkworm are secreted as pauci-mannose type N-glycans without sialic acid or galactose residues. Sialic acid on N-glycans plays important roles in protein functions. Therefore, we developed pathways for galactosylation and sialylation in silkworm. Sialylated N-glycans on proteins were successfully produced in silkworm by co-expressing galactosyltransferase and sialyltransferase and providing an external supply of a sialylation-related substrate...
February 9, 2018: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/29423671/the-glycosyltransferase-st6gal-i-is-enriched-in-cancer-stem-like-cells-in-colorectal-carcinoma-and-contributes-to-their-chemo-resistance
#6
H Cui, S Yang, Y Jiang, C Li, Y Zhao, Y Shi, Y Hao, F Qian, B Tang, P Yu
PURPOSE: Presence of cancer stem cells (CSCs) contributes to tumor outgrowth, chemo-resistance and relapse in some cancers including colorectal carcinoma (CRC). The current characterization methods of CSCs in CRC only allows enrichment of CSCs but not their purification. Recent reports showed that ST6 beta-galactoside alpha-2,6-sialyltransferase 1 (ST6Gal-I) plays an essential role in protecting tumor cells against harsh environment like oxidative stress and nutrient deprivation. Therefore, whether ST6Gal-I may be highly expressed in CSCs or whether it may enhance resistance of tumor cells to chemotherapy deserves exploration...
February 8, 2018: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29423033/prognostic-significance-of-st6galnac-1-expression-in-patients-with-non-metastatic-clear-cell-renal-cell-carcinoma
#7
Qi Bai, Li Liu, Wei Xi, Jiajun Wang, Yu Xia, Yang Qu, Ying Xiong, Qilai Long, Jiejie Xu, Jianming Guo
Background: Sialyltransferase ST6GalNAc-1 is highly expressed in tumor cells and associated with tumor aggressiveness and poor prognosis. In the present study, we aimed to investigate the clinical and prognostic significance of sialyltransferase ST6GalNAc-1 in patients with non-metastatic ccRCC. Results: High expression of ST6GalNAc-1 in tumor tissue was an independent prognostic factor for overall survival (p<0.001) and recurrence free survival (p<0.001) in multivariate analysis...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29402301/sialylation-of-egfr-by-the-st6gal-i-sialyltransferase-promotes-egfr-activation-and-resistance-to-gefitinib-mediated-cell-death
#8
Colleen M Britain, Andrew T Holdbrooks, Joshua C Anderson, Christopher D Willey, Susan L Bellis
BACKGROUND: The ST6Gal-I sialyltransferase is upregulated in numerous cancers, and high expression of this enzyme correlates with poor patient prognosis in various malignancies, including ovarian cancer. Through its sialylation of a select cohort of cell surface receptors, ST6Gal-I modulates cell signaling to promote tumor cell survival. The goal of the present study was to investigate the influence of ST6Gal-I on another important receptor that controls cancer cell behavior, EGFR. Additionally, the effect of ST6Gal-I on cancer cells treated with the common EGFR inhibitor, gefitinib, was evaluated...
February 5, 2018: Journal of Ovarian Research
https://www.readbyqxmd.com/read/29353880/differential-effect-of-disease-associated-st8sia2-haplotype-on-cerebral-white-matter-diffusion-properties-in-schizophrenia-and-healthy-controls
#9
REVIEW
Janice M Fullerton, Paul Klauser, Rhoshel K Lenroot, Alex D Shaw, Bronwyn Overs, Anna Heath, Murray J Cairns, Joshua Atkins, Rodney Scott, Peter R Schofield, Cyndi Shannon Weickert, Christos Pantelis, Alex Fornito, Thomas J Whitford, Thomas W Weickert, Andrew Zalesky
Brain white matter abnormalities are evident in individuals with schizophrenia, and also their first-degree relatives, suggesting that some alterations may relate to underlying genetic risk. The ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) gene, which encodes the alpha-2,8-sialyltransferase 8B enzyme that aids neuronal migration and synaptic plasticity, was previously implicated as a schizophrenia susceptibility gene. This study examined the extent to which specific haplotypes in ST8SIA2 influence white matter microstructure using diffusion-weighted imaging of individuals with schizophrenia (n = 281) and healthy controls (n = 172), recruited across five Australian sites...
January 22, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29348846/st6galnac1-plays-important-roles-in-enhancing-cancer-stem-phenotypes-of-colorectal-cancer-via-the-akt-pathway
#10
Tadashi Ogawa, Yoshihiko Hirohashi, Aiko Murai, Toshihiko Nishidate, Kenji Okita, Liming Wang, Yuzuru Ikehara, Tetsuta Satoyoshi, Akihiro Usui, Terufumi Kubo, Munehide Nakastugawa, Takayuki Kanaseki, Tomohide Tsukahara, Goro Kutomi, Tomohisa Furuhata, Koichi Hirata, Noriyuki Sato, Toru Mizuguchi, Ichiro Takemasa, Toshihiko Torigoe
Colorectal cancer (CRC) is a mortal disease due to treatment resistance, recurrence and distant metastasis. Emerging evidence has revealed that a small sub-population of cancer cells termed cancer stem cells (CSCs)/ cancer-initiating cells (CICs) is endowed with high levels of tumor-initiating ability, self-renewal ability and differentiation ability and is responsible for treatment resistance, recurrence and distant metastasis. Eradication of CSCs/CICs is essential to improve current treatments. However, the molecular mechanisms by which CSCs/CICs are maintained are still elusive...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29344148/identification-of-potentially-critical-differentially-methylated-genes-in-nasopharyngeal-carcinoma-a-comprehensive-analysis-of-methylation-profiling-and-gene-expression-profiling
#11
Lian Hui, Jingru Zhang, Xiaoxu Ding, Xing Guo, Xuejun Jang
The present study aimed to identify potentially critical differentially methylated genes associated with the progression of nasopharyngeal carcinoma (NPC). Methylation profiling data of GSE62336 deposited in the Gene Expression Omnibus database were used to identify differentially methylated regions (DMRs) and differentially methylated CpG islands (DMIs). Concurrently, differentially expressed genes (DEGs) were identified using a meta-analysis of three gene expression datasets (GSE53819, GSE13597 and GSE12452)...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29251719/expression-system-for-structural-and-functional-studies-of-human-glycosylation-enzymes
#12
Kelley W Moremen, Annapoorani Ramiah, Melissa Stuart, Jason Steel, Lu Meng, Farhad Forouhar, Heather A Moniz, Gagandeep Gahlay, Zhongwei Gao, Digantkumar Chapla, Shuo Wang, Jeong-Yeh Yang, Pradeep Kumar Prabhakar, Roy Johnson, Mitche Dela Rosa, Christoph Geisler, Alison V Nairn, Jayaraman Seetharaman, Sheng-Cheng Wu, Liang Tong, Harry J Gilbert, Joshua LaBaer, Donald L Jarvis
Vertebrate glycoproteins and glycolipids are synthesized in complex biosynthetic pathways localized predominantly within membrane compartments of the secretory pathway. The enzymes that catalyze these reactions are exquisitely specific, yet few have been extensively characterized because of challenges associated with their recombinant expression as functional products. We used a modular approach to create an expression vector library encoding all known human glycosyltransferases, glycoside hydrolases, and sulfotransferases, as well as other glycan-modifying enzymes...
December 18, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/29247593/solid-phase-enzymatic-remodeling-produces-high-yields-of-single-glycoform-antibodies
#13
Venkata S Tayi, Michael Butler
Antibodies are synthesized in mammalian cell culture as heterogeneous mixtures of glycoforms. Production of single glycoforms remains a challenge despite their value as therapeutics. We report a method of sequential enzymatic-based changes to antibodies while immobilized on an affinity column. Various antibodies (monoclonal and polyclonal) were isolated on Protein A or G columns and their glycans modified by sequential addition of enzymes for a desired transformation. Galactosylated antibodies (>90% yield) were produced by a one stage reaction process with sialidase to remove any sialic acid residues and addition of galactose with galactosyltransferase and UDP-Gal...
December 16, 2017: Biotechnology Journal
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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...
November 2017: Xenotransplantation
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