Evidence map›Paper›PMID 24582434›Full record

ArticleStructure (London, England : 1993)2014

Structural insights into the inhibition of Wnt signaling by cancer antigen 5T4/Wnt-activated inhibitory factor 1.

Yuguang Zhao, Tomas Malinauskas, Karl Harlos, E Yvonne Jones

Open access · bronzeAbstract read
In one paragraph

Article in Structure (London, England : 1993), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

25 citing papers in PubMed, 53 citations in OpenAlex.

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  19. Cancer stem cell mobilization and therapeutic targeting of the 5T4 oncofetal antigen.Therapeutic advances in vaccines and immunotherapy · 2019
    Review
  20. Expression of Oncofetal Antigen 5T4 in Murine Taste Papillae.Frontiers in cellular neuroscience · 2019
    Article
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 2 institutions in 1 country.

Yuguang ZhaoDivision of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
Tomas MalinauskasDivision of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
Karl HarlosDivision of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
E Yvonne JonesDivision of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK. Electronic address: yvonne@strubi.ox.ac.uk.
Centre for Human Genetics · GBUniversity of Oxford · GB

Funding

Cancer Research UK 10976Cancer Research UK 17721Medical Research Council G9900061Wellcome Trust 090532
6 · The paper itself

Abstract

The tumor antigen 5T4/WAIF1 (Wnt-activated inhibitory factor 1; also known as Trophoblast glycoprotein TPBG) is a cell surface protein targeted in multiple cancer immunotherapy clinical trials. Recently, it has been shown that 5T4/WAIF1 inhibits Wnt/β-catenin signaling, a signaling system central to many developmental and pathological processes. Wnt/β-catenin signaling is controlled by multiple inhibitors and activators. Here, we report crystal structures for the extracellular domain of 5T4/WAIF1 at 1.8 Å resolution. They reveal a highly glycosylated, rigid core, comprising eight leucine-rich repeats (LRRs), which serves as a platform to present evolutionarily conserved surface residues in the N-terminal LRR1. Structural and cell-based analyses, coupled with previously reported in vivo data, suggest that Tyr325 plus the LRR1 surface centered on a second exposed aromatic residue, Phe97, are essential for inhibition of Wnt/β-catenin signaling. These results provide a structural basis for the development of 5T4/WAIF1-targeted therapies that preserve or block 5T4/WAIF1-mediated inhibition of Wnt/β-catenin signaling.

Indexed as

Gene Expression Regulation, NeoplasticAmino Acid Sequencebeta CateninConserved SequenceCrystallography, X-RayGene ExpressionHEK293 CellsHumansHydrophobic and Hydrophilic InteractionsLeucine-Rich Repeat ProteinsMembrane GlycoproteinsModels, MolecularMolecular Sequence DataProtein BindingProteinsProtein Structure, Secondarybeta CateninLeucine-Rich Repeat ProteinsMembrane GlycoproteinsProteinstrophoblastic glycoprotein 5T4, human

Identifiers

PMID24582434
PMCPMC3988984
OpenAlexW1974688346

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.