Imperial College London

DrArmandoDel Rio Hernandez

Faculty of EngineeringDepartment of Bioengineering

Senior Lecturer
 
 
 
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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{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},
title = {ATRA mechanically reprograms pancreatic stellatecells to suppress matrix remodelling and inhibitcancer cell invasion},
url = {http://dx.doi.org/10.1038/ncomms12630},
volume = {7},
year = {2016}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a dismalsurvival rate. Persistent activation of pancreatic stellate cells (PSCs) can perturb thebiomechanical homoeostasis of the tumour microenvironment to favour cancer cell invasion.Here we report that ATRA, an active metabolite of vitamin A, restores mechanical quiescencein PSCs via a mechanism involving a retinoic acid receptor beta (RAR-b)-dependentdownregulation of actomyosin (MLC-2) contractility. We show that ATRA reduces the abilityof PSCs to generate high traction forces and adapt to extracellular mechanical cues(mechanosensing), as well as suppresses force-mediated extracellular matrix remodelling toinhibit local cancer cell invasion in 3D organotypic models. Our findings implicate aRAR-b/MLC-2 pathway in peritumoural stromal remodelling and mechanosensory-drivenactivation of PSCs, and further suggest that mechanical reprogramming of PSCs with retinoicacid derivatives might be a viable alternative to stromal ablation strategies for the treatmentof 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
PY - 2016///
SN - 2041-1723
TI - ATRA mechanically reprograms pancreatic stellatecells to suppress matrix remodelling and inhibitcancer cell invasion
T2 - Nature Communications
UR - http://dx.doi.org/10.1038/ncomms12630
UR - http://hdl.handle.net/10044/1/39259
VL - 7
ER -