Evidence map›Paper›PMID 30538117›Full record

ArticleEMBO reports2019

GPER is a mechanoregulator of pancreatic stellate cells and the tumor microenvironment.

Ernesto Cortes, Muge Sarper, Benjamin Robinson, Dariusz Lachowski, Antonios Chronopoulos, Stephen D Thorpe, David A Lee, Armando E Del Río Hernández

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

Article in EMBO reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 1 pooled it
5.2field-weighted citation impact, top 4% 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

54 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. GPER: An Estrogen Receptor Key in Metastasis and Tumoral Microenvironments.International journal of molecular sciences · 2023
    Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Ernesto CortesCellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Imperial College London, London, UK.
Muge SarperCellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Imperial College London, London, UK.
Benjamin RobinsonCellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Imperial College London, London, UK.
Dariusz LachowskiCellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Imperial College London, London, UK.ORCID 0000-0003-1194-8019
Antonios ChronopoulosCellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Imperial College London, London, UK.
Stephen D ThorpeInstitute of Bioengineering, School of Engineering and Materials Science, Queen Mary University of London, London, UK s.thorpe@qmul.ac.uk a.del-rio-hernandez@imperial.ac.uk.
David A LeeInstitute of Bioengineering, School of Engineering and Materials Science, Queen Mary University of London, London, UK.ORCID 0000-0001-7646-4643
Armando E Del Río HernándezCellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Imperial College London, London, UK s.thorpe@qmul.ac.uk a.del-rio-hernandez@imperial.ac.uk.ORCID 0000-0001-5062-8910
Imperial College London · GBQueen Mary University of London · GB

Funding

Biotechnology and Biological Sciences Research Council BB/N018532/1European Research Council 282051
6 · The paper itself

Abstract

The mechanical properties of the tumor microenvironment are emerging as attractive targets for the development of therapies. Tamoxifen, an agonist of the G protein-coupled estrogen receptor (GPER), is widely used to treat estrogen-positive breast cancer. Here, we show that tamoxifen mechanically reprograms the tumor microenvironment through a newly identified GPER-mediated mechanism. Tamoxifen inhibits the myofibroblastic differentiation of pancreatic stellate cells (PSCs) in the tumor microenvironment of pancreatic cancer in an acto-myosin-dependent manner via RhoA-mediated contractility, YAP deactivation, and GPER signaling. This hampers the ability of PSCs to remodel the extracellular matrix and to promote cancer cell invasion. Tamoxifen also reduces the recruitment and polarization to the M2 phenotype of tumor-associated macrophages. Our results highlight GPER as a mechanical regulator of the tumor microenvironment that targets the three hallmarks of pancreatic cancer: desmoplasia, inflammation, and immune suppression. The well-established safety of tamoxifen in clinics may offer the possibility to redirect the singular focus of tamoxifen on the cancer cells to the greater tumor microenvironment and lead a new strategy of drug repurposing.

Indexed as

Adaptor Proteins, Signal TransducingCell DifferentiationCell Line, TumorCell PolarityHumansInflammationMacrophagesMechanotransduction, CellularNeoplasm InvasivenessPancreatic NeoplasmsPancreatic Stellate CellsPhosphoproteinsReceptors, EstrogenReceptors, G-Protein-CoupledTamoxifenTranscription FactorsAdaptor Proteins, Signal TransducingGPER1 protein, humanPhosphoproteinsReceptors, EstrogenReceptors, G-Protein-CoupledTamoxifenTranscription FactorsYAP1 protein, humanYAP-Signaling ProteinsGPERmechanotransductionRhoA signalingtamoxifentumor microenvironment

Identifiers

PMID30538117
PMCPMC6322386
OpenAlexW2904083423

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.