Imperial College London
Alternate

DrArmandoDel Rio Hernandez

Faculty of Engineering, Department of Bioengineering

Reader in Cellular and Molecular Mechanotransduction
 
 
 
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Contact

 

+44 (0)20 7594 5187a.del-rio-hernandez

 
 
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Location

 

308Bessemer BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Cortes:2019:10.15252/embr.201846556,
author = {Cortes, E and Sarper, M and Robinson, B and Lachowski, D and Chronopoulos, A and Thorpe, SD and Lee, DA and Del, Río Hernández AE},
doi = {10.15252/embr.201846556},
journal = {EMBO Reports},
title = {GPER is a mechanoregulator of pancreatic stellate cells and the tumor microenvironment},
url = {http://dx.doi.org/10.15252/embr.201846556},
volume = {20},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The 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.
AU  - Cortes,E
AU  - Sarper,M
AU  - Robinson,B
AU  - Lachowski,D
AU  - Chronopoulos,A
AU  - Thorpe,SD
AU  - Lee,DA
AU  - Del,Río Hernández AE
DO  - 10.15252/embr.201846556
PY  - 2019///
SN  - 1469-221X
TI  - GPER is a mechanoregulator of pancreatic stellate cells and the tumor microenvironment
T2  - EMBO Reports
UR  - http://dx.doi.org/10.15252/embr.201846556
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30538117
UR  - http://hdl.handle.net/10044/1/65774
VL  - 20
ER  -
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