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GPER Activation Inhibits Cancer Cell Mechanotransduction and Basement Membrane Invasion via RhoA. | LitMetric

GPER Activation Inhibits Cancer Cell Mechanotransduction and Basement Membrane Invasion via RhoA.

Cancers (Basel)

Cellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Faculty of Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.

Published: January 2020

AI Article Synopsis

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073197PMC
http://dx.doi.org/10.3390/cancers12020289DOI Listing

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