Evidence map›Paper›PMID 25868729›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015

A common sugar-nucleotide-mediated mechanism of inhibition of (glycosamino)glycan biosynthesis, as evidenced by 6F-GalNAc (Ac3).

Xander M van Wijk, Roger Lawrence, Victor L Thijssen, Sebastiaan A van den Broek, Ran Troost, Monique van Scherpenzeel, Natasha Naidu, Arie Oosterhof, Arjan W Griffioen, Dirk J Lefeber and 2 more

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In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.3field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 33 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 6 institutions in 2 countries.

Xander M van Wijk*Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Department of Synthetic Organic Chemistry, Institute for Molecules and Materials, and Department of Neurology, Laboratory for Genetic, Endocrine and Metabolic Disease, Radboud University Medical Centre, Nijmegen, The Netherlands; Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, and Glycotechnology Core, University of California San Diego, San Diego, California, USA; and Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Centre, Amsterdam, The Netherlands.
Roger Lawrence*Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Department of Synthetic Organic Chemistry, Institute for Molecules and Materials, and Department of Neurology, Laboratory for Genetic, Endocrine and Metabolic Disease, Radboud University Medical Centre, Nijmegen, The Netherlands; Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, and Glycotechnology Core, University of California San Diego, San Diego, California, USA; and Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Centre, Amsterdam, The Netherlands.
Victor L Thijssen*Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Department of Synthetic Organic Chemistry, Institute for Molecules and Materials, and Department of Neurology, Laboratory for Genetic, Endocrine and Metabolic Disease, Radboud University Medical Centre, Nijmegen, The Netherlands; Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, and Glycotechnology Core, University of California San Diego, San Diego, California, USA; and Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Centre, Amsterdam, The Netherlands.
Sebastiaan A van den Broek*Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Department of Synthetic Organic Chemistry, Institute for Molecules and Materials, and Department of Neurology, Laboratory for Genetic, Endocrine and Metabolic Disease, Radboud University Medical Centre, Nijmegen, The Netherlands; Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, and Glycotechnology Core, University of California San Diego, San Diego, California, USA; and Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Centre, Amsterdam, The Netherlands.
Ran Troost*Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Department of Synthetic Organic Chemistry, Institute for Molecules and Materials, and Department of Neurology, Laboratory for Genetic, Endocrine and Metabolic Disease, Radboud University Medical Centre, Nijmegen, The Netherlands; Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, and Glycotechnology Core, University of California San Diego, San Diego, California, USA; and Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Centre, Amsterdam, The Netherlands.
Monique van Scherpenzeel*Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Department of Synthetic Organic Chemistry, Institute for Molecules and Materials, and Department of Neurology, Laboratory for Genetic, Endocrine and Metabolic Disease, Radboud University Medical Centre, Nijmegen, The Netherlands; Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, and Glycotechnology Core, University of California San Diego, San Diego, California, USA; and Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Centre, Amsterdam, The Netherlands.
Natasha Naidu*Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Department of Synthetic Organic Chemistry, Institute for Molecules and Materials, and Department of Neurology, Laboratory for Genetic, Endocrine and Metabolic Disease, Radboud University Medical Centre, Nijmegen, The Netherlands; Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, and Glycotechnology Core, University of California San Diego, San Diego, California, USA; and Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Centre, Amsterdam, The Netherlands.
Arie Oosterhof*Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Department of Synthetic Organic Chemistry, Institute for Molecules and Materials, and Department of Neurology, Laboratory for Genetic, Endocrine and Metabolic Disease, Radboud University Medical Centre, Nijmegen, The Netherlands; Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, and Glycotechnology Core, University of California San Diego, San Diego, California, USA; and Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Centre, Amsterdam, The Netherlands.
Arjan W Griffioen*Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Department of Synthetic Organic Chemistry, Institute for Molecules and Materials, and Department of Neurology, Laboratory for Genetic, Endocrine and Metabolic Disease, Radboud University Medical Centre, Nijmegen, The Netherlands; Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, and Glycotechnology Core, University of California San Diego, San Diego, California, USA; and Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Centre, Amsterdam, The Netherlands.
Dirk J Lefeber*Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Department of Synthetic Organic Chemistry, Institute for Molecules and Materials, and Department of Neurology, Laboratory for Genetic, Endocrine and Metabolic Disease, Radboud University Medical Centre, Nijmegen, The Netherlands; Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, and Glycotechnology Core, University of California San Diego, San Diego, California, USA; and Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Centre, Amsterdam, The Netherlands.
Floris L van Delft*Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Department of Synthetic Organic Chemistry, Institute for Molecules and Materials, and Department of Neurology, Laboratory for Genetic, Endocrine and Metabolic Disease, Radboud University Medical Centre, Nijmegen, The Netherlands; Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, and Glycotechnology Core, University of California San Diego, San Diego, California, USA; and Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Centre, Amsterdam, The Netherlands.
Toin H van Kuppevelt*Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Department of Synthetic Organic Chemistry, Institute for Molecules and Materials, and Department of Neurology, Laboratory for Genetic, Endocrine and Metabolic Disease, Radboud University Medical Centre, Nijmegen, The Netherlands; Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, and Glycotechnology Core, University of California San Diego, San Diego, California, USA; and Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Centre, Amsterdam, The Netherlands toin.vankuppevelt@radboudumc.nl.
Radboud University Medical Center · NLAmsterdam UMC Location VUmc · NLRadboud Institute for Molecular Life Sciences · NLRadboud University Nijmegen · NLUniversity of California, San Diego · USUniversity of San Diego · US

Funding

Structure and Function of 3-O-sulfation in Heparan SulfateR01GM093131 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ESKO, JEFFREY D · 2010 to 2013
$1.2M
NIGMS NIH HHS GM093131NIGMS NIH HHS R01 GM093131
6 · The paper itself

Abstract

Glycosaminoglycan (GAG) polysaccharides have been implicated in a variety of cellular processes, and alterations in their amount and structure have been associated with diseases such as cancer. In this study, we probed 11 sugar analogs for their capacity to interfere with GAG biosynthesis. One analog, with a modification not directly involved in the glycosidic bond formation, 6F-N-acetyl-d-galactosamine (GalNAc) (Ac3), was selected for further study on its metabolic and biologic effect. Treatment of human ovarian carcinoma cells with 50 μM 6F-GalNAc (Ac3) inhibited biosynthesis of GAGs (chondroitin/dermatan sulfate by ∼50-60%, heparan sulfate by ∼35%), N-acetyl-d-glucosamine (GlcNAc)/GalNAc containing glycans recognized by the lectins Datura stramonium and peanut agglutinin (by ∼74 and ∼43%, respectively), and O-GlcNAc protein modification. With respect to function, 6F-GalNAc (Ac3) treatment inhibited growth factor signaling and reduced in vivo angiogenesis by ∼33%. Although the analog was readily transformed in cells into the uridine 5'-diphosphate (UDP)-activated form, it was not incorporated into GAGs. Rather, it strongly reduced cellular UDP-GalNAc and UDP-GlcNAc pools. Together with data from the literature, these findings indicate that nucleotide sugar depletion without incorporation is a common mechanism of sugar analogs for inhibiting GAG/glycan biosynthesis.

Indexed as

AcetylgalactosamineAnimalsCell LineChick EmbryoFibroblast Growth Factor 2GlycosaminoglycansHeLa CellsHumansHuman Umbilical Vein Endothelial CellsNeovascularization, PhysiologicPolysaccharidesSignal TransductionStructure-Activity RelationshipUridine Diphosphate N-AcetylgalactosamineUridine Diphosphate N-AcetylglucosamineVascular Endothelial Growth Factor AAcetylgalactosamineFibroblast Growth Factor 2GlycosaminoglycansPolysaccharidesUridine Diphosphate N-AcetylgalactosamineUridine Diphosphate N-AcetylglucosamineVascular Endothelial Growth Factor AVEGFA protein, humanangiogenesisglycobiologygrowth factor signalingsugar analog

Identifiers

PMID25868729
PMCPMC4478805
OpenAlexW2076526241

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.