Evidence map›Paper›PMID 27185050›Full record

ArticleScientific reports2016

Epitope mapping by a Wnt-blocking antibody: evidence of the Wnt binding domain in heparan sulfate.

Wei Gao, Yongmei Xu, Jian Liu, Mitchell Ho

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
2.1field-weighted citation impact, top 15% 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

45 citing papers in PubMed, 56 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Myeloid deficiency of heparan sulfate 6-O-endosulfatases impairs bone marrow hematopoiesis.Matrix biology : journal of the International Society for Matrix Biology · 2024
    Article
  10. Article
  11. Article
  12. Article
  13. Heparan sulfate promotes TRAIL-induced tumor cell apoptosis.bioRxiv : the preprint server for biology · 2023
    Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Computationally guided conversion of the specificity of E-selectin to mimic that of Siglec-8.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  20. Role of glypican-1 in regulating multiple cellular signaling pathways.American journal of physiology. Cell physiology · 2021
    Review
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

4 authors at 3 institutions in 2 countries.

Wei GaoLaboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Yongmei XuDivision of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
Jian LiuDivision of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
Mitchell HoLaboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
University of North Carolina at Chapel Hill · USCenter for Cancer Research · USNational Institutes of Health · US

Funding

Development of new antibody-based cancer therapiesZIABC010891 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HO, MITCHELL · 2009 to 2025
$21.4M
In vitro synthesis of recombinant heparan sulfateR01HL094463 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LIU, JIAN, PAWLINSKI, RAFAL L · 2009 to 2021
$5.2M
Uncovering the controlling mechanisms in heparan sulfate biosynthesisU01GM102137 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LIU, JIAN · 2013 to 2016
$1.2M
Antibody Therapy of CancerZ01BC010891 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HO, MITCHELL · 2008 to 2008
$56k
Intramural NIH HHS Z01 BC010891Intramural NIH HHS ZIA BC010891NHLBI NIH HHS R01 HL094463NIGMS NIH HHS U01 GM102137
6 · The paper itself

Abstract

Heparan sulfate (HS) is a polysaccharide known to modulate many important biological processes, including Wnt signaling. However, the biochemical interaction between HS and Wnt molecules is not well characterized largely due to the lack of suitable methods. To determine the Wnt binding domain in HS, we used a Wnt signaling-inhibitory antibody (HS20) and a panel of synthetic HS oligosaccharides with distinct lengths and sulfation modifications. We found that the binding of HS20 to heparan sulfate required sulfation at both the C2 position (2-O-sulfation) and C6 position (6-O-sulfation). The oligosaccharides with the greatest competitive effect for HS20 binding were between six and eight saccharide residues in length. Additionally, a four residue-long oligosaccharide could also be recognized by HS20 if an additional 3-O-sulfation modification was present. Furthermore, similar oligosaccharides with 2-O, 6-O and 3-O-sulfations showed inhibition for Wnt activation. These results have revealed that HS20 and Wnt recognize a HS structure containing IdoA2S and GlcNS6S, and that the 3-O-sulfation in GlcNS6S3S significantly enhances the binding of both HS20 and Wnt. This study provides the evidence for identifying the Wnt binding domain in HS and suggests a therapeutic approach to target the interaction of Wnt and HS in cancer and other diseases.

Indexed as

AnimalsAntibodies, BlockingAntibodies, MonoclonalAntibody SpecificityBinding SitesCarbohydrate SequenceCell LineCHO CellsCricetulusEpitope MappingGlypicansHeparan SulfateHumansL CellsMiceOligosaccharidesAntibodies, BlockingAntibodies, MonoclonalGlypicansGPC3 protein, humanHeparan SulfateOligosaccharidesWnt Proteins

Identifiers

PMID27185050
PMCPMC4869111
OpenAlexW2398571812

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.