Evidence map›Paper›PMID 22926518›Full record

ArticleOncogene2013

Specific interactions between Smad proteins and AP-1 components determine TGFβ-induced breast cancer cell invasion.

A Sundqvist, A Zieba, E Vasilaki, C Herrera Hidalgo, O Söderberg, D Koinuma, K Miyazono, C-H Heldin, U Landegren, P Ten Dijke and 1 more

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
5.2field-weighted citation impact, top 3% 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

62 citing papers in PubMed, 106 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. ModelingJournal of the American Heart Association · 2025
    Article
  8. Article
  9. Article
  10. Analysis of the DNA-binding properties of TGF-β-activated Smad complexes unveils a possible molecular basis for cellular context-dependent signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
  11. Article
  12. Article
  13. Article
  14. FRA-1 as a Regulator of EMT and Metastasis in Breast Cancer.International journal of molecular sciences · 2023
    Review
  15. Article
  16. Review
  17. TGF-β in developmental and fibrogenic EMTs.Seminars in cancer biology · 2022
    Review
  18. Review
  19. Matrix Metalloproteinase-10 in Kidney Injury Repair and Disease.International journal of molecular sciences · 2022
    Review
  20. Article

2 more citing papers are in PubMed but not listed here.

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 4 institutions in 3 countries.

A SundqvistLudwig Institute for Cancer Research, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
A Zieba
E Vasilaki
C Herrera Hidalgo
O Söderberg
D Koinuma
K Miyazono
C-H Heldin
U Landegren
P Ten Dijke
H van Dam
Uppsala University · SELudwig Cancer Research · SEScience for Life Laboratory · SEThe University of Tokyo · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Deregulation of the transforming growth factor β (TGFβ) signal transduction cascade is functionally linked to cancer. In early phases, TGFβ acts as a tumor suppressor by inhibiting tumor cell proliferation, whereas in late phases, it can act as a tumor promoter by stimulating tumor cell invasion and metastasis. Smad transcriptional effectors mediate TGFβ responses, but relatively little is known about the Smad-containing complexes that are important for epithelial-mesenchymal transition and invasion. In this study, we have tested the hypothesis that specific members of the AP-1 transcription factor family determine TGFβ signaling specificity in breast cancer cell invasion. Using a 3D model of collagen-embedded spheroids of MCF10A-MII premalignant human breast cancer cells, we identified the AP-1 transcription factor components c-Jun, JunB, c-Fos and Fra1 as essential factors for TGFβ-induced invasion and found that various mesenchymal and invasion-associated TGFβ-induced genes are co-regulated by these proteins. In situ proximity ligation assays showed that TGFβ signaling not only induces complexes between Smad3 and Smad4 in the nucleus but also complexes between Smad2/3 and Fra1, whereas complexes between Smad3, c-Jun and JunB could already be detected before TGFβ stimulation. Finally, chromatin immunoprecipitations showed that c-Jun, JunB and Fra1, but not c-Fos, are required for TGFβ-induced binding of Smad2/3 to the mmp-10 and pai-1 promoters. Together these results suggest that in particular formation of Smad2/3-Fra1 complexes may reflect activation of the Smad/AP-1-dependent TGFβ-induced invasion program.

Indexed as

Breast NeoplasmsCell Line, TumorEnzyme ActivationFos-Related Antigen 1HumansMatrix MetalloproteinasesMesodermNeoplasm InvasivenessPlasminogen Activator Inhibitor 1Promoter Regions, GeneticProtein BindingProtein Serine-Threonine KinasesProto-Oncogene Proteins c-fosProto-Oncogene Proteins c-junReceptors, Transforming Growth Factor betaReceptor, Transforming Growth Factor-beta Type IFos-Related Antigen 1JunB protein, humanMatrix MetalloproteinasesPlasminogen Activator Inhibitor 1Protein Serine-Threonine KinasesProto-Oncogene Proteins c-fosProto-Oncogene Proteins c-junReceptors, Transforming Growth Factor betaReceptor, Transforming Growth Factor-beta Type ISmad ProteinsTranscription Factor AP-1Transcription FactorsTransforming Growth Factor beta

Identifiers

PMID22926518
OpenAlexW2033964863

What OpenQuestion holds

Textmetadata
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.