Evidence map›Paper›PMID 30538116›Full record

ArticleEMBO reports2019

Tamoxifen mechanically reprograms the tumor microenvironment via HIF-1A and reduces cancer cell survival.

Ernesto Cortes, Dariusz Lachowski, Benjamin Robinson, Muge Sarper, Jaakko S Teppo, Stephen D Thorpe, Tyler J Lieberthal, Kazunari Iwamoto, David A Lee, Mariko Okada-Hatakeyama and 2 more

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 49 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 3 pooled it
2.5field-weighted citation impact, top 10% 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

49 citing papers in PubMed, 3 syntheses or guidelines pooled it, 82 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 3 countries.

Ernesto CortesCellular 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
Benjamin RobinsonCellular 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.
Jaakko S TeppoInstitute of Biotechnology, University of Helsinki, Helsinki, Finland.ORCID 0000-0003-1022-5572
Stephen D ThorpeInstitute of Bioengineering, School of Engineering and Materials Science, Queen Mary University of London, London, UK.
Tyler J LieberthalCellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Imperial College London, London, UK.
Kazunari IwamotoLaboratory of Cell Systems, Institute for Protein Research, Osaka University, Suita, Osaka, Japan.
David A LeeInstitute of Bioengineering, School of Engineering and Materials Science, Queen Mary University of London, London, UK.ORCID 0000-0001-7646-4643
Mariko Okada-HatakeyamaLaboratory of Cell Systems, Institute for Protein Research, Osaka University, Suita, Osaka, Japan.
Markku T VarjosaloInstitute of Biotechnology, University of Helsinki, Helsinki, Finland.
Armando E Del Río HernándezCellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Imperial College London, London, UK a.del-rio-hernandez@imperial.ac.uk.ORCID 0000-0001-5062-8910
Imperial College London · GBQueen Mary University of London · GBRIKEN Center for Integrative Medical Sciences · JPUniversity of Helsinki · FI

Funding

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

Abstract

The tumor microenvironment is fundamental to cancer progression, and the influence of its mechanical properties is increasingly being appreciated. Tamoxifen has been used for many years to treat estrogen-positive breast cancer. Here we report that tamoxifen regulates the level and activity of collagen cross-linking and degradative enzymes, and hence the organization of the extracellular matrix, via a mechanism involving both the G protein-coupled estrogen receptor (GPER) and hypoxia-inducible factor-1 alpha (HIF-1A). We show that tamoxifen reduces HIF-1A levels by suppressing myosin-dependent contractility and matrix stiffness mechanosensing. Tamoxifen also downregulates hypoxia-regulated genes and increases vascularization in PDAC tissues. Our findings implicate the GPER/HIF-1A axis as a master regulator of peri-tumoral stromal remodeling and the fibrovascular tumor microenvironment and offer a paradigm shift for tamoxifen from a well-established drug in breast cancer hormonal therapy to an alternative candidate for stromal targeting strategies in PDAC and possibly other cancers.

Indexed as

AdenocarcinomaAnimalsCarcinoma, Pancreatic DuctalCell Line, TumorCell SurvivalCellular ReprogrammingFibroblastsGene Expression Regulation, NeoplasticHumansHypoxia-Inducible Factor 1, alpha SubunitMiceMyosinsNeovascularization, PathologicReceptors, EstrogenReceptors, G-Protein-CoupledSignal TransductionGPER1 protein, humanHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitMyosinsReceptors, EstrogenReceptors, G-Protein-CoupledTamoxifenGPERHIF‐1Atamoxifentumor microenvironment

Identifiers

PMID30538116
PMCPMC6322388
OpenAlexW2904780544

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.