Evidence map›Paper›PMID 20428185›Full record

ArticleThe Journal of investigative dermatology2010

PAI-1 mediates the TGF-beta1+EGF-induced "scatter" response in transformed human keratinocytes.

Jennifer Freytag, Cynthia E Wilkins-Port, Craig E Higgins, Stephen P Higgins, Rohan Samarakoon, Paul J Higgins

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of investigative dermatology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

36 citing papers in PubMed, 50 citations in OpenAlex.

  1. Plasminogen activator inhibitor-1 promotes the proliferation and blocks TGF-β1-dependent growth inhibition of cholesteatoma keratinocytes by ERK signaling.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026
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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

6 authors at 1 institution in 1 country.

Jennifer FreytagCenter for Cell Biology and Cancer Research, Albany Medical College, Albany, New York 12208, USA.
Cynthia E Wilkins-Port
Craig E Higgins
Stephen P Higgins
Rohan Samarakoon
Paul J Higgins
Albany Medical Center Hospital · US

Funding

MATRIX MEDIATORS OF WOUND HEALINGR01GM057242 · NIGMS · WEILL MEDICAL COLLEGE OF CORNELL UNIV · PI HIGGINS, PAUL J. · 1998 to 2010
$3.2M
NIGMS NIH HHS GM57242NIGMS NIH HHS R01 GM057242
6 · The paper itself

Abstract

Cooperative interactions between growth factor signaling pathways are important elements in carcinoma progression. A model system combining transforming growth factor-beta1 (TGF-beta1) and EGF was developed to investigate mechanisms underlying induced epithelial-to-mesenchymal transition (EMT) in ras-transformed human (HaCaT II-4) keratinocytes. Dual stimulation with TGF-beta1+EGF resulted in keratinocyte "plasticity" and pronounced colony dispersal. The most highly expressed transcript, identified by mRNA profiling, encoded plasminogen activator inhibitor-1 (PAI-1; SERPINE1). PAI-1 negatively regulates plasmin-dependent matrix degradation, preserving a stromal scaffold permissive for keratinocyte motility. Mitogen-activated extracellular kinase (MEK)/extracellular signal-regulated kinase (ERK) and p38 signaling were required for maximal PAI-1 upregulation and TGF-beta1+EGF-stimulated cell locomotion, as pharmacologic disruption of MEK/p38 activity ablated both responses. Moreover, PAI-1 knockdown alone effectively inhibited TGF-beta1+EGF-dependent cell scattering, indicating a functional role for this SERPIN in the dual-growth factor model of induced motility. Moreover, EGFR signaling blockade or EGFR knockdown attenuated TGF-beta1-induced PAI-1 expression, implicating EGFR transactivation in TGF-beta1-stimulated PAI-1 expression, and reduced colony dispersal in TGF-beta1+EGF-treated cultures. Identification of such cooperative signaling networks and their effect on specific invasion-promoting target genes, such as PAI-1, may lead to the development of pathway-specific therapeutics that affect late-stage events in human tumor progression.

Indexed as

Cell DifferentiationCell Line, TransformedEpithelial CellsErbB ReceptorsExtracellular Signal-Regulated MAP KinasesHumansKeratinocytesMAP Kinase Kinase 1MAP Kinase Signaling SystemMesodermp38 Mitogen-Activated Protein KinasesPhosphorylationPlasminogen Activator Inhibitor 1Transforming Growth Factor beta1Up-RegulationEGFR protein, humanErbB ReceptorsExtracellular Signal-Regulated MAP KinasesMAP Kinase Kinase 1p38 Mitogen-Activated Protein KinasesPlasminogen Activator Inhibitor 1Transforming Growth Factor beta1

Identifiers

PMID20428185
PMCPMC3774605
OpenAlexW2044461696

What OpenQuestion holds

Textmetadata
LicenceTDM
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.