Evidence map›Paper›PMID 27566553›Full record

ArticleOncotarget2016

TGFβ upregulates PAR-1 expression and signalling responses in A549 lung adenocarcinoma cells.

Natalia Smoktunowicz, Manuela Platé, Alejandro Ortiz Stern, Vanessa D'Antongiovanni, Eifion Robinson, Vijay Chudasama, Stephen Caddick, Chris J Scotton, Gabor Jarai, Rachel C Chambers

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

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
0.3field-weighted citation impact, top 31% 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

16 citing papers in PubMed, 34 citations in OpenAlex.

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  14. Glial ACells · 2020
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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

10 authors at 3 institutions in 1 country.

Natalia SmoktunowiczCentre for Inflammation and Tissue Repair, UCL Respiratory, University College London, London, UK.
Manuela PlatéCentre for Inflammation and Tissue Repair, UCL Respiratory, University College London, London, UK.
Alejandro Ortiz SternCentre for Inflammation and Tissue Repair, UCL Respiratory, University College London, London, UK.
Vanessa D'AntongiovanniCentre for Inflammation and Tissue Repair, UCL Respiratory, University College London, London, UK.
Eifion RobinsonDepartment of Chemistry, University College London, London, UK.
Vijay ChudasamaDepartment of Chemistry, University College London, London, UK.
Stephen CaddickDepartment of Chemistry, University College London, London, UK.
Chris J ScottonCentre for Inflammation and Tissue Repair, UCL Respiratory, University College London, London, UK.
Gabor JaraiNovartis Institutes of Biomedical Research, Horsham, UK.
Rachel C ChambersCentre for Inflammation and Tissue Repair, UCL Respiratory, University College London, London, UK.
University College London · GBCentre for Inflammation Research · GBNovartis (United Kingdom) · GB

Funding

Medical Research Council G0800340
6 · The paper itself

Abstract

The major high-affinity thrombin receptor, proteinase activated receptor-1 (PAR-1) is expressed at low levels by the normal epithelium but is upregulated in many types of cancer, including lung cancer. The thrombin-PAR-1 signalling axis contributes to the activation of latent TGFβ in response to tissue injury via an αvβ6 integrin-mediated mechanism. TGFβ is a pleiotropic cytokine that acts as a tumour suppressor in normal and dysplastic cells but switches into a tumour promoter in advanced tumours. In this study we demonstrate that TGFβ is a positive regulator of PAR-1 expression in A549 lung adenocarcinoma cells, which in turn increases the sensitivity of these cells to thrombin signalling. We further demonstrate that this effect is Smad3-, ERK1/2- and Sp1-dependent. We also show that TGFβ-mediated PAR-1 upregulation is accompanied by increased expression of integrin αv and β6 subunits. Finally, TGFβ pre-stimulation promotes increased migratory potential of A549 to thrombin. These data have important implications for our understanding of the interplay between coagulation and TGFβ signalling responses in lung cancer.

Indexed as

A549 CellsAdenocarcinomaBlood CoagulationCell MovementGene Expression Regulation, NeoplasticHumansIntegrin alpha5Integrin beta ChainsLung NeoplasmsMAP Kinase Signaling SystemProtein KinasesReceptor, PAR-1Smad3 ProteinThrombinTransforming Growth Factor betaUp-RegulationIntegrin alpha5integrin beta6Integrin beta ChainsProtein KinasesReceptor, PAR-1Smad3 ProteinSMAD3 protein, humanSp1 kinaseThrombinTransforming Growth Factor betacancerPAR-1TGFβthrombin

Identifiers

PMID27566553
PMCPMC5323169
OpenAlexW2516260084

What OpenQuestion holds

Textmetadata
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.