Evidence map›Paper›PMID 16741576›Full record

ArticleThe Journal of clinical investigation2006

Autocrine PDGFR signaling promotes mammary cancer metastasis.

Martin Jechlinger, Andreas Sommer, Richard Moriggl, Peter Seither, Norbert Kraut, Paola Capodiecci, Michael Donovan, Carlos Cordon-Cardo, Hartmut Beug, Stefan Grünert

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 195 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
195citing papers in PubMed, 1 pooled it
9.8field-weighted citation impact, top 1% 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

195 citing papers in PubMed, 1 synthesis or guideline pooled it, 372 citations in OpenAlex.

  1. Pooled it
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  11. The atypical KRASMolecular oncology · 2025
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135 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

10 authors at 1 institution in 1 country.

Martin JechlingerResearch Institute for Molecular Pathology, Vienna, Austria.
Andreas Sommer
Richard Moriggl
Peter Seither
Norbert Kraut
Paola Capodiecci
Michael Donovan
Carlos Cordon-Cardo
Hartmut Beug
Stefan Grünert
Research Institute of Molecular Pathology · AT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Metastasis is the major cause of cancer morbidity, but strategies for direct interference with invasion processes are lacking. Dedifferentiated, late-stage tumor cells secrete multiple factors that represent attractive targets for therapeutic intervention. Here we show that metastatic potential of oncogenic mammary epithelial cells requires an autocrine PDGF/PDGFR loop, which is established as a consequence of TGF-beta-induced epithelial-mesenchymal transition (EMT), a faithful in vitro correlate of metastasis. The cooperation of autocrine PDGFR signaling with oncogenic Ras hyperactivates PI3K and is required for survival during EMT. Autocrine PDGFR signaling also contributes to maintenance of EMT, possibly through activation of STAT1 and other distinct pathways. Inhibition of PDGFR signaling interfered with EMT and caused apoptosis in murine and human mammary carcinoma cell lines. Consequently, overexpression of a dominant-negative PDGFR or application of the established cancer drug STI571 interfered with experimental metastasis in mice. Similarly, in mouse mammary tumor virus-Neu (MMTV-Neu) transgenic mice, TGF-beta enhanced metastasis of mammary tumors, induced EMT, and elevated PDGFR signaling. Finally, expression of PDGFRalpha and -beta correlated with invasive behavior in human mammary carcinomas. Thus, autocrine PDGFR signaling plays an essential role during cancer progression, suggesting a novel application of STI571 to therapeutically interfere with metastasis.

Indexed as

Autocrine CommunicationBreast NeoplasmsMammary Neoplasms, ExperimentalNeoplasm MetastasisAnimalsAntineoplastic AgentsApoptosisBenzamidesCell DifferentiationCell Line, TumorEnzyme ActivationEpithelial CellsFemaleHumansImatinib MesylateMammary Tumor Virus, MouseAntineoplastic AgentsBenzamidesImatinib MesylatePhosphatidylinositol 3-KinasesPiperazinesProtein Kinase InhibitorsPyrimidinesras ProteinsReceptor, Platelet-Derived Growth Factor alphaReceptor, Platelet-Derived Growth Factor betaRecombinant Fusion ProteinsTransforming Growth Factor beta

Identifiers

PMID16741576
PMCPMC1469776
OpenAlexW2009863423

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.