Evidence map›Paper›PMID 30641926›Full record

ArticleCells2019

Altered VEGF Splicing Isoform Balance in Tumor Endothelium Involves Activation of Splicing Factors Srpk1 and Srsf1 by the Wilms' Tumor Suppressor Wt1.

Kay-Dietrich Wagner, Mounir El Maï, Michael Ladomery, Tareg Belali, Nathalie Leccia, Jean-François Michiels, Nicole Wagner

Open access · goldAbstract read
In one paragraph

Article in Cells, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 2 pooled it
2.6field-weighted citation impact, top 10% 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

32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 49 citations in OpenAlex.

  1. Pooled it
  2. Alternative splicing and cancer: a systematic review.Signal transduction and targeted therapy · 2021
    Pooled it
  3. Review
  4. Splicing to orchestrate cell fate.Molecular therapy. Nucleic acids · 2025
    Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. SRPKs: a promising therapeutic target in cancer.Clinical and experimental medicine · 2023
    Review
  12. Review
  13. Cardiomyocyte-Specific Wt1 Is Involved in Cardiac Metabolism and Response to Damage.Journal of cardiovascular development and disease · 2023
    Article
  14. P16INK4A-More Than a Senescence Marker.Life (Basel, Switzerland) · 2022
    Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. 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

7 authors at 3 institutions in 2 countries.

Kay-Dietrich WagnerUniversité Côte d'Azur, Institute of Biology Valrose, Nice (iBV), CNRS UMR7277, INSERM U1091, 06107 Nice, France. kwagner@unice.fr.ORCID 0000-0001-5483-7760
Mounir El MaïUniversité Côte d'Azur, Institute for Research on Cancer and Aging, Nice (IRCAN), CNRS UMR7284/INSERM U1081, 06107 Nice, France. elmai_mounir@yahoo.fr.ORCID 0000-0002-7528-2474
Michael LadomeryFaculty of Health and Applied Sciences, University of the West of England, Bristol BS16 1QY, UK. Michael.Ladomery@uwe.ac.uk.
Tareg BelaliFaculty of Health and Applied Sciences, University of the West of England, Bristol BS16 1QY, UK. Tareg.Belali@uwe.ac.uk.
Nathalie LecciaDepartment of Pathology, CHU Nice, 06107 Nice, France. leccia.n@chu-nice.fr.
Jean-François MichielsDepartment of Pathology, CHU Nice, 06107 Nice, France. michiels.jf@chu-nice.fr.
Nicole WagnerUniversité Côte d'Azur, Institute of Biology Valrose, Nice (iBV), CNRS UMR7277, INSERM U1091, 06107 Nice, France. nwagner@unice.fr.ORCID 0000-0002-2746-0707
Centre National de la Recherche Scientifique · FRCentre Hospitalier Universitaire de Nice · FRUniversity of the West of England · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Angiogenesis is one hallmark of cancer. Vascular endothelial growth factor (VEGF) is a known inducer of angiogenesis. Many patients benefit from antiangiogenic therapies, which however have limitations. Although VEGF is overexpressed in most tumors, different VEGF isoforms with distinct angiogenic properties are produced through alternative splicing. In podocytes, the Wilms' tumor suppressor 1 (WT1) suppresses the Serine/arginine-rich protein-specific splicing factor kinase (SRPK1), and indirectly Serine/arginine-rich splicing factor 1 (Srsf1) activity, and alters VEGF splicing. We analyzed VEGF isoforms, Wt1, Srpk1, and Srsf1 in normal and tumor endothelium. Wt1, Srpk1, Srsf1, and the angiogenic VEGF164a isoform were highly expressed in tumor endothelium compared to normal lung endothelium. Nuclear expression of Srsf1 was detectable in the endothelium of various tumor types, but not in healthy tissues. Inducible conditional vessel-specific knockout of Wt1 reduced Wt1, Srpk1, and Srsf1 expression in endothelial cells and induced a shift towards the antiangiogenic VEGF120 isoform. Wt1(-KTS) directly binds and activates both the promoters of Srpk1 and Srsf1 in endothelial cells. In conclusion, Wt1 activates Srpk1 and Srsf1 and induces expression of angiogenic VEGF isoforms in tumor endothelium.

Indexed as

Alternative SplicingAnimalsCell Line, TumorEndothelium, VascularFemaleLung NeoplasmsMaleMiceMice, Inbred C57BLNeovascularization, PathologicProtein Serine-Threonine KinasesRepressor ProteinsSerine-Arginine Splicing FactorsVascular Endothelial Growth Factor AWilms TumorWT1 ProteinsProtein Serine-Threonine KinasesRepressor ProteinsSerine-Arginine Splicing FactorsSrpk1 protein, mouseSrsf1 protein, mouseVascular Endothelial Growth Factor Avascular endothelial growth factor A, mouseWT1 protein, mouseWT1 Proteinsendotheliumsplicing factorstranscriptional regulationVEGF isoformsWilms’ tumor suppressor Wt1

Identifiers

PMID30641926
PMCPMC6356959
OpenAlexW2910775861

What OpenQuestion holds

Textmetadata
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.