Evidence map›Paper›PMID 29858602›Full record

ArticleOncogene2018

Protective effect of stromal Dickkopf-3 in prostate cancer: opposing roles for TGFBI and ECM-1.

Zainab Al Shareef, Hoda Kardooni, Virginia Murillo-Garzón, Giacomo Domenici, Emmanouil Stylianakis, Jennifer H Steel, Miriam Rabano, Irantzu Gorroño-Etxebarria, Ignacio Zabalza, Maria dM Vivanco and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 1 pooled it
2.0field-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

48 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.

  1. Pooled it
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  7. Review
  8. Article
  9. Article
  10. Article
  11. Osteoblast-Derived ECM1 Promotes Anti-Androgen Resistance in Bone Metastatic Prostate Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  12. Article
  13. Translational andrology and urology · 2024
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 2 countries.

Zainab Al ShareefDepartment of Surgery and Cancer, Imperial College London, London, UK.
Hoda KardooniDepartment of Surgery and Cancer, Imperial College London, London, UK.
Virginia Murillo-GarzónCenter for Cooperative Research in Biosciences, CIC bioGUNE, Derio, Spain.
Giacomo DomeniciCenter for Cooperative Research in Biosciences, CIC bioGUNE, Derio, Spain.
Emmanouil StylianakisDepartment of Surgery and Cancer, Imperial College London, London, UK.
Jennifer H SteelDepartment of Surgery and Cancer, Imperial College London, London, UK.ORCID http://orcid.org/0000-0003-4439-0090
Miriam RabanoCenter for Cooperative Research in Biosciences, CIC bioGUNE, Derio, Spain.
Irantzu Gorroño-EtxebarriaCenter for Cooperative Research in Biosciences, CIC bioGUNE, Derio, Spain.
Ignacio ZabalzaDepartment of Pathology, Galdakao-Usansolo Hospital, Galdakao, Spain.
Maria dM VivancoCenter for Cooperative Research in Biosciences, CIC bioGUNE, Derio, Spain.
Jonathan WaxmanDepartment of Surgery and Cancer, Imperial College London, London, UK.
Robert M KyptaDepartment of Surgery and Cancer, Imperial College London, London, UK. r.kypta@imperial.ac.uk.
CIC bioGUNE · ESImperial College London · GBHospital de Galdakao · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Aberrant transforming growth factor-β (TGF-β) signaling is a hallmark of the stromal microenvironment in cancer. Dickkopf-3 (Dkk-3), shown to inhibit TGF-β signaling, is downregulated in prostate cancer and upregulated in the stroma in benign prostatic hyperplasia, but the function of stromal Dkk-3 is unclear. Here we show that DKK3 silencing in WPMY-1 prostate stromal cells increases TGF-β signaling activity and that stromal cell-conditioned media inhibit prostate cancer cell invasion in a Dkk-3-dependent manner. DKK3 silencing increased the level of the cell-adhesion regulator TGF-β-induced protein (TGFBI) in stromal and epithelial cell-conditioned media, and recombinant TGFBI increased prostate cancer cell invasion. Reduced expression of Dkk-3 in patient tumors was associated with increased expression of TGFBI. DKK3 silencing reduced the level of extracellular matrix protein-1 (ECM-1) in prostate stromal cell-conditioned media but increased it in epithelial cell-conditioned media, and recombinant ECM-1 inhibited TGFBI-induced prostate cancer cell invasion. Increased ECM1 and DKK3 mRNA expression in prostate tumors was associated with increased relapse-free survival. These observations are consistent with a model in which the loss of Dkk-3 in prostate cancer leads to increased secretion of TGFBI and ECM-1, which have tumor-promoting and tumor-protective roles, respectively. Determining how the balance between the opposing roles of extracellular factors influences prostate carcinogenesis will be key to developing therapies that target the tumor microenvironment.

Indexed as

Adaptor Proteins, Signal TransducingChemokinesExtracellular Matrix ProteinsHumansIntercellular Signaling Peptides and ProteinsMaleProstatic NeoplasmsTransforming Growth Factor beta1Tumor MicroenvironmentAdaptor Proteins, Signal TransducingChemokinesDKK3 protein, humanECM1 protein, humanExtracellular Matrix ProteinsIntercellular Signaling Peptides and ProteinsTGFB1 protein, humanTransforming Growth Factor beta1

Identifiers

PMID29858602
PMCPMC6160402
OpenAlexW2805200921

What OpenQuestion holds

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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.