Imperial College London
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DrJoseCortes Lopez

Faculty of Engineering, Department of Bioengineering

 
 
 
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Contact

 

+44 (0)7944 338 144j.e.corteslopez Website

 
 
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Location

 

B-122Bessemer BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Cortes:2018:10.1038/s41388-018-0631-3,
author = {Cortes, E and Lachowski, D and Rice, A and Thorpe, SD and Robinson, B and Yeldag, G and Lee, DA and Ghemtio, L and Rombouts, K and Del, Río Hernández AE},
doi = {10.1038/s41388-018-0631-3},
journal = {Oncogene},
pages = {2910--2922},
title = {Tamoxifen mechanically deactivates hepatic stellate cells via the G protein-coupled estrogen receptor},
url = {http://dx.doi.org/10.1038/s41388-018-0631-3},
volume = {38},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Tamoxifen has been used for many years to target estrogen receptor signalling in breast cancer cells. Tamoxifen is also an agonist of the G protein-coupled estrogen receptor (GPER), a GPCR ubiquitously expressed in tissues that mediates the acute response to estrogens. Here we report that tamoxifen promotes mechanical quiescence in hepatic stellate cells (HSCs), stromal fibroblast-like cells whose activation triggers and perpetuates liver fibrosis in hepatocellular carcinomas. This mechanical deactivation is mediated by the GPER/RhoA/myosin axis and induces YAP deactivation. We report that tamoxifen decreases the levels of hypoxia-inducible factor-1 alpha (HIF-1α) and the synthesis of extracellular matrix proteins through a mechanical mechanism that involves actomyosin-dependent contractility and mechanosensing of tissue stiffness. Our results implicate GPER-mediated estrogen signalling in the mechanosensory-driven activation of HSCs and put forward estrogenic signalling as an option for mechanical reprogramming of myofibroblast-like cells in the tumour microenvironment. Tamoxifen, with half a century of safe clinical use, might lead this strategy of drug repositioning.
AU  - Cortes,E
AU  - Lachowski,D
AU  - Rice,A
AU  - Thorpe,SD
AU  - Robinson,B
AU  - Yeldag,G
AU  - Lee,DA
AU  - Ghemtio,L
AU  - Rombouts,K
AU  - Del,Río Hernández AE
DO  - 10.1038/s41388-018-0631-3
EP  - 2922
PY  - 2018///
SN  - 0950-9232
SP  - 2910
TI  - Tamoxifen mechanically deactivates hepatic stellate cells via the G protein-coupled estrogen receptor
T2  - Oncogene
UR  - http://dx.doi.org/10.1038/s41388-018-0631-3
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30575816
UR  - http://hdl.handle.net/10044/1/66570
VL  - 38
ER  -
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