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.201846557,
author = {Cortes, E and Lachowski, D and Robinson, B and Sarper, M and Teppo, JS and Thorpe, SD and Lieberthal, TJ and Iwamoto, K and Lee, DA and Okada-Hatakeyama, M and Varjosalo, MT and Del, Río Hernández AE},
doi = {10.15252/embr.201846557},
journal = {EMBO Reports},
title = {Tamoxifen mechanically reprograms the tumor microenvironment via HIF-1A and reduces cancer cell survival},
url = {http://dx.doi.org/10.15252/embr.201846557},
volume = {20},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The tumor microenvironment is fundamental to cancer progression, and the influence of its mechanical properties is increasingly being appreciated. Tamoxifen has been used for many years to treat estrogen-positive breast cancer. Here we report that tamoxifen regulates the level and activity of collagen cross-linking and degradative enzymes, and hence the organization of the extracellular matrix, via a mechanism involving both the G protein-coupled estrogen receptor (GPER) and hypoxia-inducible factor-1 alpha (HIF-1A). We show that tamoxifen reduces HIF-1A levels by suppressing myosin-dependent contractility and matrix stiffness mechanosensing. Tamoxifen also downregulates hypoxia-regulated genes and increases vascularization in PDAC tissues. Our findings implicate the GPER/HIF-1A axis as a master regulator of peri-tumoral stromal remodeling and the fibrovascular tumor microenvironment and offer a paradigm shift for tamoxifen from a well-established drug in breast cancer hormonal therapy to an alternative candidate for stromal targeting strategies in PDAC and possibly other cancers.
AU  - Cortes,E
AU  - Lachowski,D
AU  - Robinson,B
AU  - Sarper,M
AU  - Teppo,JS
AU  - Thorpe,SD
AU  - Lieberthal,TJ
AU  - Iwamoto,K
AU  - Lee,DA
AU  - Okada-Hatakeyama,M
AU  - Varjosalo,MT
AU  - Del,Río Hernández AE
DO  - 10.15252/embr.201846557
PY  - 2019///
SN  - 1469-221X
TI  - Tamoxifen mechanically reprograms the tumor microenvironment via HIF-1A and reduces cancer cell survival
T2  - EMBO Reports
UR  - http://dx.doi.org/10.15252/embr.201846557
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30538116
UR  - http://hdl.handle.net/10044/1/65773
VL  - 20
ER  -
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