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https://www.readbyqxmd.com/read/27871859/alpha2-3-sialyltransferase-iii-knockdown-sensitized-ovarian-cancer-cells-to-cisplatin-induced-apoptosis
#1
Xiaoyu Wang, Yiting Zhang, Haiyingjie Lin, Yan Liu, Yi Tan, Jie Lin, Fenze Gao, Shaoqiang Lin
Emerging evidence indicates that β-galactoside-α2,3-sialyltransferase III (ST3Gal3) involves in development, inflammation, neoplastic transformation, and metastasis. However, the role of ST3Gal3 in regulating cancer chemoresistance remains elusive. Herein, we investigated the functional effects of ST3Gal3 in cisplatin-resistant ovarian cancer cells. We found that the levels of ST3Gal3 mRNA differed significantly among ovarian cancer cell lines. HO8910PM cells that have high invasive and metastatic capacity express elevated ST3Gal3 mRNA and are resistant to cisplatin, comparing to SKOV3 cells that have a lower level of ST3Gal3 expression and are more chemosensitive to cisplatin...
November 18, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27835877/o-glycan-sialylation-alters-galectin-3-subcellular-localization-and-decreases-chemotherapy-sensitivity-in-gastric-cancer
#2
Sofia N Santos, Mara S Junqueira, Guilherme Francisco, Manuel Vilanova, Ana Magalhães, Marcelo Dias Baruffi, Roger Chammas, Adrian L Harris, Celso A Reis, Emerson S Bernardes
ST6GalNAc-I, the sialyltransferase responsible for sialyl-Tn (sTn) synthesis, has been previously reported to be positively associated with cancer aggressiveness. Here we describe a novel sTn-dependent mechanism for chemotherapeutic resistance. We show that sTn protects cancer cells against chemotherapeutic-induced cell death by decreasing the interaction of cell surface glycan receptors with galectin-3 and increasing its intracellular accumulation. Moreover, exogenously added galectin-3 potentiated the chemotherapeutics-induced cytotoxicity in sTn non-expressing cells, while sTn overexpressing cells were protected...
November 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27821620/tnf-up-regulates-st3gal4-and-sialyl-lewisx-expression-in-lung-epithelial-cells-through-an-intronic-atf2-responsive-element
#3
Florent Colomb, Marie-Ange Krzewinski-Recchi, Agata Steenackers, Audrey Vincent, Anne Harduin-Lepers, Philippe Delannoy, Sophie Groux-Degroote
We have previously shown that TNF induced the up-regulation of the sialyltransferase gene ST3GAL4 BX transcript through mitogen- and stress-activated kinase 1/2 (MSK1/2), extracellular-signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) signaling pathways. This up-regulation resulted in sialyl-Lewis(x) (sLe(x)) over-expression on high-molecular weight glycoproteins in inflamed airway epithelium and increased the adhesion of Pseudomonas aeruginosa PAO1 and PAK strains to lung epithelial cells...
November 7, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27820809/regulation-of-autoantibody-activity-by-the-il-23-th17-axis-determines-the-onset-of-autoimmune-disease
#4
René Pfeifle, Tobias Rothe, Natacha Ipseiz, Hans U Scherer, Stephan Culemann, Ulrike Harre, Jochen A Ackermann, Martina Seefried, Arnd Kleyer, Stefan Uderhardt, Benjamin Haugg, Axel J Hueber, Patrick Daum, Gordon F Heidkamp, Changrong Ge, Sybille Böhm, Anja Lux, Wolfgang Schuh, Iryna Magorivska, Kutty S Nandakumar, Erik Lönnblom, Christoph Becker, Diana Dudziak, Manfred Wuhrer, Yoann Rombouts, Carolien A Koeleman, René Toes, Thomas H Winkler, Rikard Holmdahl, Martin Herrmann, Stephan Blüml, Falk Nimmerjahn, Georg Schett, Gerhard Krönke
The checkpoints and mechanisms that contribute to autoantibody-driven disease are as yet incompletely understood. Here we identified the axis of interleukin 23 (IL-23) and the TH17 subset of helper T cells as a decisive factor that controlled the intrinsic inflammatory activity of autoantibodies and triggered the clinical onset of autoimmune arthritis. By instructing B cells in an IL-22- and IL-21-dependent manner, TH17 cells regulated the expression of β-galactoside α2,6-sialyltransferase 1 in newly differentiating antibody-producing cells and determined the glycosylation profile and activity of immunoglobulin G (IgG) produced by the plasma cells that subsequently emerged...
November 7, 2016: Nature Immunology
https://www.readbyqxmd.com/read/27807044/golgi-enzymes-do-not-cycle-through-the-endoplasmic-reticulum-during-protein-secretion-or-mitosis
#5
Julien Villeneuve, Juan Duran, Margherita Scarpa, Laia Bassaganyas, Josse Van Galen, Vivek Malhotra
Golgi specific sialyltransferase (ST) expressed as a chimera with the rapamycin-binding domain of mTOR, FRB, relocates to the endoplasmic reticulum (ER) in cells exposed to rapamycin that also express invariant chain (Ii)-FKBP in the ER. This result has been taken to propose that Golgi resident enzymes cycle to the ER constitutively. We show ST-FRB is trapped in the ER even without Ii-FKBP upon rapamycin addition. This is because ER-Golgi cycling FKBP proteins contain a C-terminal KDEL-like sequence, bind ST-FRB in the Golgi and are transported together back to the ER by KDEL-receptor mediated retrograde transport...
November 2, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27798070/circulating-blood-and-platelets-supply-glycosyltransferases-that-enable-extrinsic-extracellular-glycosylation
#6
Melissa M Lee-Sundlov, David J Ashline, Andrew J Hanneman, Renata Grozovsky, Vernon N Reinhold, Karin M Hoffmeister, Joseph Ty Lau
Glycosyltransferases, usually residing within the intracellular secretory apparatus, also circulate in the blood. Many of these blood-borne glycosyltransferases are associated with pathological states, including malignancies and inflammatory conditions. Despite the potential for dynamic modifications of glycans on distal cell surfaces and in the extracellular milieu, the glycan-modifying activities present in systemic circulation have not been systematically examined. Here, we describe an evaluation of blood-borne sialyl-, galactosyl- and fucosyltransferase activities that act upon the four common terminal glycan precursor motifs, GlcNAc monomer, Gal(β3)GlcNAc, Gal(β4)GlcNAc and Gal(β3)GalNAc, to produce more complex glycan structures...
October 26, 2016: Glycobiology
https://www.readbyqxmd.com/read/27787577/alpha-n-acetyl-neuraminide-alpha-2-8-sialyltransferase-1-can-support-immune-responses-toward-tumors-overexpressing-ganglioside-d3-in-mice
#7
Jonathan M Eby, Levi Barse, Steven W Henning, Martijn J W E Rabelink, Jared Klarquist, Emily R Gilbert, Adam M Hammer, Manuel F Fernandez, Nathan Yung, Safia Khan, Hannah G Miller, Edward R Kessler, Elizabeth Garrett-Mayer, Daniel F Dilling, Rob C Hoeben, I Caroline Le Poole
An immunotherapeutic strategy is discussed supporting anti-tumor activity toward malignancies overexpressing ganglioside D3. GD3 can be targeted by NKT cells when derived moieties are presented in the context of CD1d. NKT cells can support anti-tumor responses by secreting inflammatory cytokines and through cytotoxicity toward CD1d(+)GD3(+) tumors. To overexpress GD3, we generated expression vector DNA and an adenoviral vector encoding the enzyme responsible for generating GD3 from its ubiquitous precursor GM3...
October 27, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27779707/st3gal-iii-modulates-breast-cancer-cell-adhesion-and-invasion-by-altering-the-expression-of-invasion-related-molecules
#8
Hong-Xia Cui, Honglan Wang, Yuchun Wang, Juan Song, Hua Tian, Chunhui Xia, Yetong Shen
Changes in the carbohydrate structure on the surface of tumor cells is an important feature of cancer metastasis. The specific role of sialic acids in the glycoconjugate terminal has not yet been clearly elucidated in these processes. Previously, we reported that α2,3-sialic acid residues in breast cancer are associated with metastatic potential. The α2,3-sialyltransferase ST3Gal III, which adds α2,3-sialic acids to glycoproteins, is overexpressed in various tumors, and enzyme activity is correlated with tumor metastasis, yet its mechanistic role has not been fully evaluated...
October 18, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27704662/cigarette-smoking-alters-sialylation-in-the-fallopian-tube-of-women-with-implications-for-the-pathogenesis-of-ectopic-pregnancy
#9
Junko Nio-Kobayashi, Hazirah B Z Abidin, Jeremy K Brown, Toshihiko Iwanaga, Andrew W Horne, W Colin Duncan
Sialylation creates a negative charge on the cell surface that can interfere with blastocyst implantation. For example, α2,6-sialylation on terminal galactose, catalyzed by the sialyltransferase ST6GAL1, inhibits the binding of galectin-1, a β-galactoside-binding lectin. We recently reported the potential involvement of galectin-1 and -3 in the pathogenesis of tubal ectopic pregnancy; however, the precise role of galectins and their ligand glycoconjugates remain unclear. Here, we investigated the expression of the genes encoding α2,3- and α2,6-galactoside sialyltransferases (ST3GAL1-6 and ST6GAL1-2) and the localization of sialic acids in the Fallopian tube of women with or without ectopic implantation...
October 5, 2016: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/27683310/mice-lacking-sialyltransferase-st3gal-ii-develop-late-onset-obesity-and-insulin-resistance
#10
Pablo H H Lopez, Susan Aja, Kazuhiro Aoki, Marcus M Seldin, Xia Lei, Gabriele V Ronnett, G William Wong, Ronald L Schnaar
Sialyltransferases are a family of 20 gene products in mice and humans that transfer sialic acid from its activated precursor, CMP-sialic acid, to the terminus of glycoprotein and glycolipid acceptors. ST3Gal-II (coded by the St3gal2 gene) transfers sialic acid preferentially to the 3-position of galactose on the Galβ1-3GalNAc terminus of gangliosides GM1 and GD1b to synthesize GD1a and GT1b respectively. Mice with a targeted disruption of St3gal2 unexpectedly displayed late-onset obesity and insulin resistance...
September 28, 2016: Glycobiology
https://www.readbyqxmd.com/read/27678392/advancement-of-sialyltransferase-inhibitors-therapeutic-challenges-and-opportunities
#11
Rémi Szabo, Danielle Skropeta
Hypersialylation of tumor cell surface proteins along with a marked upregulation of sialyltransferase (ST) activity is a well-established hallmark of cancer. Due to the critical role of STs in tumor growth and progression, ST inhibition has emerged as a potential new antimetastatic strategy for a range of cancers including pancreatic and ovarian. Human STs are divided into subtypes based on their linkage and acceptor molecule, with each subtype controlling the synthesis of specific sialylated structures with unique biological roles...
September 28, 2016: Medicinal Research Reviews
https://www.readbyqxmd.com/read/27644888/quantum-mechanics-molecular-mechanics-study-of-the-sialyltransferase-reaction-mechanism
#12
Yojiro Hamada, Yusuke Kanematsu, Masanori Tachikawa
The sialyltransferase is an enzyme that transfers the sialic acid moiety from cytidine 5'-monophospho-N-acetyl-neuraminic acid (CMP-NeuAc) to the terminal position of glycans. To elucidate the catalytic mechanism of sialyltransferase, we explored the potential energy surface along the sialic acid transfer reaction coordinates by the hybrid quantum mechanics/molecular mechanics method on the basis of the crystal structure of sialyltransferase CstII. Our calculation demonstrated that CstII employed an SN1-like reaction mechanism via the formation of a short-lived oxocarbenium ion intermediate...
October 11, 2016: Biochemistry
https://www.readbyqxmd.com/read/27642072/genetic-engineering-of-cho-cells-for-viral-resistance-to-minute-virus-of-mice
#13
Joaquina X Mascarenhas, Nikolay Korokhov, Lisa Burger, Ademola Kassim, Jason Tuter, Daniel Miller, Trissa Borgschulte, Henry J George, Audrey Chang, David J Pintel, David Onions, Kevin J Kayser
Contamination by the parvovirus minute virus of mice (MVM) remains a challenge in Chinese hamster ovary (CHO) biopharmaceutical production processes. Although infrequent, infection of a bioreactor can be catastrophic for a manufacturer, can impact patient drug supply and safety, and can have regulatory implications. We evaluated engineering a CHO parental cell line (CHOZN(®) GS(-/-) ) to create a new host cell line that is resistant to MVM infection by modifying the major receptors used by the virus to enter cells...
September 19, 2016: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/27614914/conformational-and-electrostatic-analysis-of-sn1-donor-analogue-glycomimetic-inhibitors-of-st3gal-i-mammalian-sialyltransferase
#14
Werner Crous, Kevin J Naidoo
Mammalian sialyltransferases play a role in the metastasis of various cancers in humans. Inhibitors of these enzymes will in principle be able to directly inhibit aberrant sialylation in cancer. Inhibitors of ST3Gal-I resembling the donor component of SN1 Transition State structures were previously evaluated as part of a kinetics study. Here, using classical dynamics simulations and free energy perturbation calculations, we rationalize the performance of three of these donor analogue ST3Gal-I enzyme inhibitors...
October 15, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27588895/altered-gene-expression-of-glycosyltransferases-and-sialyltransferases-and-total-amount-of-glycosphingolipids-following-herpes-simplex-virus-infection
#15
Kazuki Miyaji, Jun-Ichi Furukawa, Youichi Suzuki, Naoki Yamamoto, Yasuro Shinohara, Nobuhiro Yuki
There is a case report of a patient with overlapping Guillain-Barré syndrome and Bickerstaff brainstem encephalitis after infection with herpes simplex virus type 1 (HSV-1), who carried high titers of serum anti-GQ1b IgG antibodies. Several studies have linked viral infection to the modulation of ganglioside expression such as human T-lymphotropic virus to GD2 and simian virus 40 to GM3. Also, enhancement of the expression of GM2 on the cell membrane after cytomegalovirus infection has been reported. The objective of this study was to unveil the relationship between HSV-1 infection and the alteration of cellular ganglioside expression in neuronal and glial cell lines...
August 18, 2016: Carbohydrate Research
https://www.readbyqxmd.com/read/27588482/st6gal-i-overexpression-facilitates-prostate-cancer-progression-via-the-pi3k-akt-gsk-3%C3%AE-%C3%AE-catenin-signaling-pathway
#16
Anwen Wei, Bo Fan, Yujie Zhao, Han Zhang, Liping Wang, Xiao Yu, Qingmin Yuan, Deyong Yang, Shujing Wang
ST6Gal-I sialyltransferase adds α2,6-linked sialic acids to the terminal ends of glycan chains of glycoproteins and glycolipids. ST6Gal-I is reportedly upregulated in many cancers, including hepatocellular carcinoma, ovarian cancer and breast cancer. However, the expression and function of ST6Gal-I in prostate cancer (PCa) and the mechanism underlying this function remain largely unknown. In this study, we observed that ST6Gal-I expression was upregulated in human PCa tissues compared to non-malignant prostate tissues...
August 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27584569/association-of-single-nucleotide-polymorphisms-in-the-st3gal4-gene-with-vwf-antigen-and-factor-viii-activity
#17
Jaewoo Song, Cheng Xue, John S Preisser, Drake W Cramer, Katie L Houck, Guo Liu, Aaron R Folsom, David Couper, Fuli Yu, Jing-Fei Dong
VWF is extensively glycosylated with biantennary core fucosylated glycans. Most N-linked and O-linked glycans on VWF are sialylated. FVIII is also glycosylated, with a glycan structure similar to that of VWF. ST3GAL sialyltransferases catalyze the transfer of sialic acids in the α2,3 linkage to termini of N- and O-glycans. This sialic acid modification is critical for VWF synthesis and activity. We analyzed genetic and phenotypic data from the Atherosclerosis Risk in Communities (ARIC) study for the association of single nucleotide polymorphisms (SNPs) in the ST3GAL4 gene with plasma VWF levels and FVIII activity in 12,117 subjects...
2016: PloS One
https://www.readbyqxmd.com/read/27559112/silencing-of-st6gal-i-enhances-colorectal-cancer-metastasis-by-down-regulating-kai1-via-exosome-mediated-exportation-and-thereby-rescues-integrin-signaling
#18
Yu Ri Jung, Jung-Jin Park, Yeung Bae Jin, Yuan Jie Cao, Myung-Jin Park, Eun Ju Kim, Minyoung Lee
Aberrant sialylation has long been correlated with human cancer. Increased ST6 Gal I (β-galactoside α 2, 6 sialyltransferase) and consequently higher levels of cell-surface α 2, 6 sialylation has been associated with human colorectal cancer (CRC) metastasis. We have extensive circumstantial data that sialylation is connected to cancer metastasis, but we do not understand in detail how sialylation can switch on/off multiple steps in cancer metastasis. To investigate the molecular mechanism underlying the ST6Gal I-mediated metastasis of CRC, we silenced the ST6Gal I gene in a metastatic SW620 CRC cell line (SW620-shST6Gal I) and examined the metastatic behavior of the cells...
August 24, 2016: Carcinogenesis
https://www.readbyqxmd.com/read/27543325/improved-workflow-for-the-efficient-preparation-of-ready-to-use-cmp-activated-sialic-acids
#19
Pierre-André Gilormini, Cédric Lion, Maxence Noel, Marie-Ange Krzewinski-Recchi, Anne Harduin-Lepers, Yann Guérardel, Christophe Biot
Natural and synthetically modified CMP-activated sialic acids are essential research tools in the field of glycobiology: among other applications, they can be used to probe glycans, detect sialylation defects at the cell surface, or carry out detailed studies of sialyltransferase activities. However, these chemical tools are notoriously unstable because of hydrolytic decomposition, and are very time-consuming and costly to obtain. They are nigh impossible to store with satisfactory purity, and their preparation requires multiple laborious purification steps that usually lead to heavy product loss...
August 19, 2016: Glycobiology
https://www.readbyqxmd.com/read/27531903/prognostic-significance-of-st6galnac-1-expression-in-patients-with-non-metastatic-clear-cell-renal-cell-carcinoma
#20
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...
August 12, 2016: Oncotarget
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