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Matrix stiffness induces epithelial–mesenchymal transition and promotes chemoresistance in pancreatic cancer cells
Increased matrix rigidity associated with the fibrotic reaction is documented to stimulate intracellular signalling pathways that promote cancer cell survival and tumour growth. Pancreatic cancer is one of the stiffest of all human solid carcinomas and is characterised by a remarkable desmoplastic r...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5541706/ https://www.ncbi.nlm.nih.gov/pubmed/28671675 http://dx.doi.org/10.1038/oncsis.2017.54 |
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author | Rice, A J Cortes, E Lachowski, D Cheung, B C H Karim, S A Morton, J P del Río Hernández, A |
author_facet | Rice, A J Cortes, E Lachowski, D Cheung, B C H Karim, S A Morton, J P del Río Hernández, A |
author_sort | Rice, A J |
collection | PubMed |
description | Increased matrix rigidity associated with the fibrotic reaction is documented to stimulate intracellular signalling pathways that promote cancer cell survival and tumour growth. Pancreatic cancer is one of the stiffest of all human solid carcinomas and is characterised by a remarkable desmoplastic reaction. Here we use mouse models, genetically engineered to recapitulate human pancreatic cancer, and several pancreatic cancer cell lines as a model to investigate the effect of matrix stiffness in epithelial–mesenchymal transition (EMT) and resistance to chemotherapeutics. We found that recapitulation of the fibrotic rigidities found in pancreatic cancer tissues promote elements of EMT, including increases in vimentin expression, decreases in E-cadherin expression, nuclear localisation of β-catenin, YAP and TAZ and changes in cell shape towards a mesenchymal phenotype. We also report that stiffness induces chemoresistance to paclitaxel, but not to gemcitabine, both commonly used therapeutics, suggesting that environmental rigidity underlies an aspect of chemoresistance. |
format | Online Article Text |
id | pubmed-5541706 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-55417062017-08-08 Matrix stiffness induces epithelial–mesenchymal transition and promotes chemoresistance in pancreatic cancer cells Rice, A J Cortes, E Lachowski, D Cheung, B C H Karim, S A Morton, J P del Río Hernández, A Oncogenesis Original Article Increased matrix rigidity associated with the fibrotic reaction is documented to stimulate intracellular signalling pathways that promote cancer cell survival and tumour growth. Pancreatic cancer is one of the stiffest of all human solid carcinomas and is characterised by a remarkable desmoplastic reaction. Here we use mouse models, genetically engineered to recapitulate human pancreatic cancer, and several pancreatic cancer cell lines as a model to investigate the effect of matrix stiffness in epithelial–mesenchymal transition (EMT) and resistance to chemotherapeutics. We found that recapitulation of the fibrotic rigidities found in pancreatic cancer tissues promote elements of EMT, including increases in vimentin expression, decreases in E-cadherin expression, nuclear localisation of β-catenin, YAP and TAZ and changes in cell shape towards a mesenchymal phenotype. We also report that stiffness induces chemoresistance to paclitaxel, but not to gemcitabine, both commonly used therapeutics, suggesting that environmental rigidity underlies an aspect of chemoresistance. Nature Publishing Group 2017-07 2017-07-03 /pmc/articles/PMC5541706/ /pubmed/28671675 http://dx.doi.org/10.1038/oncsis.2017.54 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ Oncogenesis is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Original Article Rice, A J Cortes, E Lachowski, D Cheung, B C H Karim, S A Morton, J P del Río Hernández, A Matrix stiffness induces epithelial–mesenchymal transition and promotes chemoresistance in pancreatic cancer cells |
title | Matrix stiffness induces epithelial–mesenchymal transition and promotes chemoresistance in pancreatic cancer cells |
title_full | Matrix stiffness induces epithelial–mesenchymal transition and promotes chemoresistance in pancreatic cancer cells |
title_fullStr | Matrix stiffness induces epithelial–mesenchymal transition and promotes chemoresistance in pancreatic cancer cells |
title_full_unstemmed | Matrix stiffness induces epithelial–mesenchymal transition and promotes chemoresistance in pancreatic cancer cells |
title_short | Matrix stiffness induces epithelial–mesenchymal transition and promotes chemoresistance in pancreatic cancer cells |
title_sort | matrix stiffness induces epithelial–mesenchymal transition and promotes chemoresistance in pancreatic cancer cells |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5541706/ https://www.ncbi.nlm.nih.gov/pubmed/28671675 http://dx.doi.org/10.1038/oncsis.2017.54 |
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