Evidence map›Paper›PMID 21403839›Full record

ArticleNeoplasia (New York, N.Y.)2011

Intervening in β-catenin signaling by sulindac inhibits S100A4-dependent colon cancer metastasis.

Ulrike Stein, Franziska Arlt, Janice Smith, Ulrike Sack, Pia Herrmann, Wolfgang Walther, Margit Lemm, Iduna Fichtner, Robert H Shoemaker, Peter M Schlag

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neoplasia (New York, N.Y.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed, 1 pooled it
4.0field-weighted citation impact, top 5% 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

56 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Extracellular S100A4 as a key player in fibrotic diseases.Journal of cellular and molecular medicine · 2020
    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

10 authors at 3 institutions in 2 countries.

Ulrike SteinExperimental and Clinical Research Center, Charité University Medicine, at the Max-Delbrück-Center for Molecular Medicine, Berlin, Germany. ustein@mdc-berlin.de
Franziska Arlt
Janice Smith
Ulrike Sack
Pia Herrmann
Wolfgang Walther
Margit Lemm
Iduna Fichtner
Robert H Shoemaker
Peter M Schlag
Max Delbrück Center · DECharité - Universitätsmedizin Berlin · DEFrederick National Laboratory for Cancer Research · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Colon cancer metastasis is often associated with activation of the Wnt/β-catenin signaling pathway and high expression of the metastasis mediator S100A4. We previously demonstrated the transcriptional regulation of S100A4 by β-catenin and the importance of the interconnection of these cellular programs for metastasis. Here we probe the hypothesis that the nonsteroidal anti-inflammatory drug sulindac sulfide can inhibit colon cancer metastasis by intervening in β-catenin signaling and thereby interdicting S100A4. We treated colon cancer cell lines heterozygous for gain-of-function and wild-type β-catenin with sulindac. We analyzed sulindac's effects on β-catenin expression and subcellular localization, β-catenin binding to the T-cell factor (TCF)/S100A4 promoter complex, S100A4 promoter activity, S100A4 expression, cell motility, and proliferation. Mice intrasplenically transplanted with S100A4-overexpressing colon cancer cells were treated with sulindac. Tumor growth and metastasis, and their β-catenin and S100A4 expressions, were determined. We report the expression knockdown of β-catenin by sulindac, leading to its reduced nuclear accumulation. The binding of β-catenin to TCF was clearly lowered, resulting in reduced S100A4 promoter activity and expression. This correlated well with the inhibition of cell migration and invasion, which could be rescued by ectopic S100A4 expression. In mice, sulindac treatment resulted in reduced tumor growth in the spleen (P = .014) and decreased liver metastasis in a human colon cancer xenograft model (P = .025). Splenic tumors and liver metastases of sulindac-treated mice showed lowered β-catenin and S100A4 levels. These results suggest that modulators of β-catenin signaling such as sulindac offer potential as antimetastatic agents by interdicting S100A4 expression.

Indexed as

AnimalsAnti-Inflammatory Agents, Non-SteroidalAntineoplastic Agentsbeta CateninCell MovementColonic NeoplasmsGene Expression Regulation, NeoplasticHumansLiverMiceNeoplasm MetastasisS100 Calcium-Binding Protein A4S100 ProteinsSignal TransductionSpleenSulindacAnti-Inflammatory Agents, Non-SteroidalAntineoplastic Agentsbeta CateninS100A4 protein, humanS100 Calcium-Binding Protein A4S100 ProteinsSulindacTCF Transcription FactorsWnt Proteins

Identifiers

PMID21403839
PMCPMC3033592
OpenAlexW1278199433

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.