GPER activation inhibits cancer cell mechanotransduction and basement membrane invasion via RhoA
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- dc.contributor.author Rice, Alistair
- dc.contributor.author Cortes, Ernesto
- dc.contributor.author Lachowski, Dariusz
- dc.contributor.author Oertle, Philipp
- dc.contributor.author Matellan, Carlos
- dc.contributor.author Thorpe, Stephen D.
- dc.contributor.author Ghose, Ritobrata
- dc.contributor.author Wang, Haiyun
- dc.contributor.author Lee, David A.
- dc.contributor.author Plodinec, Marija
- dc.contributor.author del Río Hernández, Armando
- dc.date.accessioned 2020-03-17T07:33:46Z
- dc.date.available 2020-03-17T07:33:46Z
- dc.date.issued 2020
- dc.description.abstract The invasive properties of cancer cells are intimately linked to their mechanical phenotype, which can be regulated by intracellular biochemical signalling. Cell contractility, induced by mechanotransduction of a stiff fibrotic matrix, and the epithelial-mesenchymal transition (EMT) promote invasion. Metastasis involves cells pushing through the basement membrane into the stroma-both of which are altered in composition with cancer progression. Agonists of the G protein-coupled oestrogen receptor (GPER), such as tamoxifen, have been largely used in the clinic, and interest in GPER, which is abundantly expressed in tissues, has greatly increased despite a lack of understanding regarding the mechanisms which promote its multiple effects. Here, we show that specific activation of GPER inhibits EMT, mechanotransduction and cell contractility in cancer cells via the GTPase Ras homolog family member A (RhoA). We further show that GPER activation inhibits invasion through an in vitro basement membrane mimic, similar in structure to the pancreatic basement membrane that we reveal as an asymmetric bilayer, which differs in composition between healthy and cancer patients.
- dc.description.sponsorship This work has been funded by the European Research Council grant 282051. A.R. acknowledges funding from the President’s PhD scholarship at Imperial College London. M.P. and P.O. received funding from the Nanotera Project
- dc.format.mimetype application/pdf
- dc.identifier.citation Rice A, Cortes E, Lachowski D, Oertle P, Matellan C, Thorpe SD et al. GPER activation inhibits cancer cell mechanotransduction and basement membrane invasion via RhoA. Cancers (Basel). 2020 Jan 25; 12(2): pii: E289. DOI: 10.3390/cancers12020289
- dc.identifier.doi http://dx.doi.org/10.3390/cancers12020289
- dc.identifier.issn 2072-6694
- dc.identifier.uri http://hdl.handle.net/10230/43911
- dc.language.iso eng
- dc.publisher MDPI
- dc.relation.ispartof Cancers (Basel). 2020 Jan 25; 12(2): pii: E289
- dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/282051
- dc.rights © 2020 by Alistair Rice et al. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.other Proteïnes -- Investigació
- dc.subject.other Càncer
- dc.subject.other Metàstasi
- dc.subject.other Tumors
- dc.title GPER activation inhibits cancer cell mechanotransduction and basement membrane invasion via RhoA
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion