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dc.contributor.authorCortes, Een_US
dc.contributor.authorSarper, Men_US
dc.contributor.authorRobinson, Ben_US
dc.contributor.authorLachowski, Den_US
dc.contributor.authorChronopoulos, Aen_US
dc.contributor.authorThorpe, SDen_US
dc.contributor.authorLee, DAen_US
dc.contributor.authorDel Río Hernández, AEen_US
dc.date.accessioned2019-01-07T13:35:40Z
dc.date.available2018-10-23en_US
dc.date.issued2019-01en_US
dc.identifier.urihttps://qmro.qmul.ac.uk/xmlui/handle/123456789/54143
dc.description.abstractThe 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.en_US
dc.languageengen_US
dc.relation.ispartofEMBO Repen_US
dc.rightsPublished under the terms of the CC BY 4.0 license
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subjectGPERen_US
dc.subjectRhoA signalingen_US
dc.subjectmechanotransductionen_US
dc.subjecttamoxifenen_US
dc.subjecttumor microenvironmenten_US
dc.titleGPER is a mechanoregulator of pancreatic stellate cells and the tumor microenvironment.en_US
dc.typeArticle
dc.rights.holder© 2018 The Authors.
dc.identifier.doi10.15252/embr.201846556en_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/30538117en_US
pubs.issue1en_US
pubs.notesNo embargoen_US
pubs.notesPublished open access.en_US
pubs.publication-statusPublisheden_US
pubs.volume20en_US
dcterms.dateAccepted2018-10-23en_US
rioxxterms.funderDefault funderen_US
rioxxterms.identifier.projectDefault projecten_US
qmul.funderMechno-regulation of genome function to direct stem cell fate::Biotechnology and Biological Sciences Research Councilen_US


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Published under the terms of the CC BY 4.0 license
Except where otherwise noted, this item's license is described as Published under the terms of the CC BY 4.0 license