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{Chronopoulos:2016:10.1038/ncomms12630,
author = {Chronopoulos, A and Robinson, B and Sarper, M and Cortes, E and Auernheimer, V and Lachowski, D and Attwood, S and Garcia, R and Ghassemi, S and Fabry, B and Del, Rio Hernandez AE},
doi = {10.1038/ncomms12630},
journal = {Nature Communications},
pages = {1--12},
title = {ATRA mechanically reprograms pancreatic stellate cells to suppress matrix remodelling and inhibit cancer cell invasion},
url = {http://dx.doi.org/10.1038/ncomms12630},
volume = {7},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a dismal survival rate. Persistent activation of pancreatic stellate cells (PSCs) can perturb the biomechanical homoeostasis of the tumour microenvironment to favour cancer cell invasion. Here we report that ATRA, an active metabolite of vitamin A, restores mechanical quiescence in PSCs via a mechanism involving a retinoic acid receptor beta (RAR-β)-dependent downregulation of actomyosin (MLC-2) contractility. We show that ATRA reduces the ability of PSCs to generate high traction forces and adapt to extracellular mechanical cues (mechanosensing), as well as suppresses force-mediated extracellular matrix remodelling to inhibit local cancer cell invasion in 3D organotypic models. Our findings implicate a RAR-β/MLC-2 pathway in peritumoural stromal remodelling and mechanosensory-driven activation of PSCs, and further suggest that mechanical reprogramming of PSCs with retinoic acid derivatives might be a viable alternative to stromal ablation strategies for the treatment of PDAC.
AU  - Chronopoulos,A
AU  - Robinson,B
AU  - Sarper,M
AU  - Cortes,E
AU  - Auernheimer,V
AU  - Lachowski,D
AU  - Attwood,S
AU  - Garcia,R
AU  - Ghassemi,S
AU  - Fabry,B
AU  - Del,Rio Hernandez AE
DO  - 10.1038/ncomms12630
EP  - 12
PY  - 2016///
SN  - 2041-1723
SP  - 1
TI  - ATRA mechanically reprograms pancreatic stellate cells to suppress matrix remodelling and inhibit cancer cell invasion
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/ncomms12630
UR  - https://www.nature.com/articles/ncomms12630
UR  - http://hdl.handle.net/10044/1/39259
VL  - 7
ER  -
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