Evidence map›Paper›PMID 26939885›Full record

ArticleNucleic acids research2016

Structure and decoy-mediated inhibition of the SOX18/Prox1-DNA interaction.

Miriam Klaus, Nina Prokoph, Mathias Girbig, Xuecong Wang, Yong-Heng Huang, Yogesh Srivastava, Linlin Hou, Kamesh Narasimhan, Prasanna R Kolatkar, Mathias Francois and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
3.3field-weighted citation impact, top 7% 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

33 citing papers in PubMed, 55 citations in OpenAlex.

  1. Article
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  3. TOX, through a glass, darkly.Frontiers in immunology · 2025
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  10. Lymphangiogenesis in gastric cancer: function and mechanism.European journal of medical research · 2023
    Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. EGR1 Enhances Lymphangiogenesis via SOX18-Mediated Activation of JAK2/STAT3 Pathway.Computational and mathematical methods in medicine · 2022
    Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. 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

11 authors at 5 institutions in 5 countries.

Miriam KlausGenome Regulation Laboratory, Drug Discovery Pipeline, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China Institut für Chemie und Biochemie, Freie Universität Berlin, Thielallee 63, 14195 Berlin, Germany.
Nina ProkophLaboratory for Structural Biochemistry, Genome Institute of Singapore, 60 Biopolis Street, 138672 Singapore.
Mathias GirbigGenome Regulation Laboratory, Drug Discovery Pipeline, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China Institut für Chemie und Biochemie, Freie Universität Berlin, Thielallee 63, 14195 Berlin, Germany.
Xuecong WangGenome Regulation Laboratory, Drug Discovery Pipeline, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Yong-Heng HuangGenome Regulation Laboratory, Drug Discovery Pipeline, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Yogesh SrivastavaGenome Regulation Laboratory, Drug Discovery Pipeline, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Linlin HouGenome Regulation Laboratory, Drug Discovery Pipeline, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Kamesh NarasimhanLaboratory for Structural Biochemistry, Genome Institute of Singapore, 60 Biopolis Street, 138672 Singapore.
Prasanna R KolatkarQatar Biomedical Research Institute, Hamad Bin Khalifa Unversity, QatarFoundation, PO Box 5825, Doha, Qatar.
Mathias FrancoisInstitute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
Ralf JauchGenome Regulation Laboratory, Drug Discovery Pipeline, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China ralf@gibh.ac.cn.
Chinese Academy of Sciences · CNGenome Institute of Singapore · SGGuangzhou Institutes of Biomedicine and Health · CNHamad bin Khalifa University · QAUniversity of Queensland · AU

Funding

Life Science and Biomedical technology Research center at NSLS-II LSBRP41GM111244 · NIGMS · BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB · PI MCSWEENEY, SEAN · 2014 to 2018
$16.4M
Case Center for Synchrotron BiosciencesP30EB009998 · NIBIB · CASE WESTERN RESERVE UNIVERSITY · PI CHANCE, MARK R · 2009 to 2018
$8.4M
NIBIB NIH HHS P30 EB009998NIGMS NIH HHS P41 GM111244
6 · The paper itself

Abstract

The transcription factor (TF) SOX18 drives lymphatic vessel development in both embryogenesis and tumour-induced neo-lymphangiogenesis. Genetic disruption of Sox18 in a mouse model protects from tumour metastasis and established the SOX18 protein as a molecular target. Here, we report the crystal structure of the SOX18 DNA binding high-mobility group (HMG) box bound to a DNA element regulating Prox1 transcription. The crystals diffracted to 1.75Å presenting the highest resolution structure of a SOX/DNA complex presently available revealing water structure, structural adjustments at the DNA contact interface and non-canonical conformations of the DNA backbone. To explore alternatives to challenging small molecule approaches for targeting the DNA-binding activity of SOX18, we designed a set of five decoys based on modified Prox1-DNA. Four decoys potently inhibited DNA binding of SOX18 in vitro and did not interact with non-SOX TFs. Serum stability, nuclease resistance and thermal denaturation assays demonstrated that a decoy circularized with a hexaethylene glycol linker and terminal phosphorothioate modifications is most stable. This SOX decoy also interfered with the expression of a luciferase reporter under control of a SOX18-dependent VCAM1 promoter in COS7 cells. Collectively, we propose SOX decoys as potential strategy for inhibiting SOX18 activity to disrupt tumour-induced neo-lymphangiogenesis.

Indexed as

AnimalsChlorocebus aethiopsCOS CellsDNAGene Expression RegulationHomeodomain ProteinsMiceNucleic Acid ConformationOligonucleotidesProspero-Related Homeobox 1 ProteinSOXF Transcription FactorsSOX Transcription FactorsTranscription, GeneticTumor Suppressor ProteinsDNAHomeodomain ProteinsOligonucleotidesProspero-Related Homeobox 1 ProteinSox18 protein, mouseSOXF Transcription FactorsSOX Transcription FactorsTumor Suppressor Proteins

Identifiers

PMID26939885
PMCPMC4856986
OpenAlexW2312974281

What OpenQuestion holds

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LicenceCC BY-NC
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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.