ER-Stress-Induced Differentiation Sensitizes Colon Cancer Stem Cells to Chemotherapy
Colon cancer stem cells (colon-CSCs) are more resistant to conventional chemotherapy than differentiated cancer cells. This subset of therapy refractory cells is therefore believed to play an important role in post-therapeutic tumor relapse. In order to improve the rate of sustained response to conv...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2015-10-01
|
Series: | Cell Reports |
Online Access: | http://www.sciencedirect.com/science/article/pii/S221112471501027X |
id |
doaj-86d9380850ce4b839880c31d6b8772ed |
---|---|
record_format |
Article |
spelling |
doaj-86d9380850ce4b839880c31d6b8772ed2020-11-24T22:11:34ZengElsevierCell Reports2211-12472015-10-0113348949410.1016/j.celrep.2015.09.016ER-Stress-Induced Differentiation Sensitizes Colon Cancer Stem Cells to ChemotherapyMattheus C.B. Wielenga0Selcuk Colak1Jarom Heijmans2Jooske F. van Lidth de Jeude3Hans M. Rodermond4James C. Paton5Adrienne W. Paton6Louis Vermeulen7Jan Paul Medema8Gijs R. van den Brink9Tytgat Institute for Liver and Intestinal Research and Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 AZ Amsterdam, the NetherlandsLaboratory of Experimental Oncology and Radiobiology, Academic Medical Center, 1105 AZ Amsterdam, the NetherlandsTytgat Institute for Liver and Intestinal Research and Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 AZ Amsterdam, the NetherlandsTytgat Institute for Liver and Intestinal Research and Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 AZ Amsterdam, the NetherlandsLaboratory of Experimental Oncology and Radiobiology, Academic Medical Center, 1105 AZ Amsterdam, the NetherlandsResearch Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, South Australia 5005, AustraliaResearch Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, South Australia 5005, AustraliaLaboratory of Experimental Oncology and Radiobiology, Academic Medical Center, 1105 AZ Amsterdam, the NetherlandsLaboratory of Experimental Oncology and Radiobiology, Academic Medical Center, 1105 AZ Amsterdam, the NetherlandsTytgat Institute for Liver and Intestinal Research and Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 AZ Amsterdam, the NetherlandsColon cancer stem cells (colon-CSCs) are more resistant to conventional chemotherapy than differentiated cancer cells. This subset of therapy refractory cells is therefore believed to play an important role in post-therapeutic tumor relapse. In order to improve the rate of sustained response to conventional chemotherapy, development of approaches is warranted that specifically sensitize colon-CSCs to treatment. Here, we report that ER-stress-induced activation of the unfolded protein response (UPR) forces colon-CSCs to differentiate, resulting in their enhanced sensitivity to chemotherapy in vitro and in vivo. Our data suggest that agents that induce activation of the UPR may be used to specifically increase sensitivity of colon-CSCs to the effects of conventional chemotherapy.http://www.sciencedirect.com/science/article/pii/S221112471501027X |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mattheus C.B. Wielenga Selcuk Colak Jarom Heijmans Jooske F. van Lidth de Jeude Hans M. Rodermond James C. Paton Adrienne W. Paton Louis Vermeulen Jan Paul Medema Gijs R. van den Brink |
spellingShingle |
Mattheus C.B. Wielenga Selcuk Colak Jarom Heijmans Jooske F. van Lidth de Jeude Hans M. Rodermond James C. Paton Adrienne W. Paton Louis Vermeulen Jan Paul Medema Gijs R. van den Brink ER-Stress-Induced Differentiation Sensitizes Colon Cancer Stem Cells to Chemotherapy Cell Reports |
author_facet |
Mattheus C.B. Wielenga Selcuk Colak Jarom Heijmans Jooske F. van Lidth de Jeude Hans M. Rodermond James C. Paton Adrienne W. Paton Louis Vermeulen Jan Paul Medema Gijs R. van den Brink |
author_sort |
Mattheus C.B. Wielenga |
title |
ER-Stress-Induced Differentiation Sensitizes Colon Cancer Stem Cells to Chemotherapy |
title_short |
ER-Stress-Induced Differentiation Sensitizes Colon Cancer Stem Cells to Chemotherapy |
title_full |
ER-Stress-Induced Differentiation Sensitizes Colon Cancer Stem Cells to Chemotherapy |
title_fullStr |
ER-Stress-Induced Differentiation Sensitizes Colon Cancer Stem Cells to Chemotherapy |
title_full_unstemmed |
ER-Stress-Induced Differentiation Sensitizes Colon Cancer Stem Cells to Chemotherapy |
title_sort |
er-stress-induced differentiation sensitizes colon cancer stem cells to chemotherapy |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2015-10-01 |
description |
Colon cancer stem cells (colon-CSCs) are more resistant to conventional chemotherapy than differentiated cancer cells. This subset of therapy refractory cells is therefore believed to play an important role in post-therapeutic tumor relapse. In order to improve the rate of sustained response to conventional chemotherapy, development of approaches is warranted that specifically sensitize colon-CSCs to treatment. Here, we report that ER-stress-induced activation of the unfolded protein response (UPR) forces colon-CSCs to differentiate, resulting in their enhanced sensitivity to chemotherapy in vitro and in vivo. Our data suggest that agents that induce activation of the UPR may be used to specifically increase sensitivity of colon-CSCs to the effects of conventional chemotherapy. |
url |
http://www.sciencedirect.com/science/article/pii/S221112471501027X |
work_keys_str_mv |
AT mattheuscbwielenga erstressinduceddifferentiationsensitizescoloncancerstemcellstochemotherapy AT selcukcolak erstressinduceddifferentiationsensitizescoloncancerstemcellstochemotherapy AT jaromheijmans erstressinduceddifferentiationsensitizescoloncancerstemcellstochemotherapy AT jooskefvanlidthdejeude erstressinduceddifferentiationsensitizescoloncancerstemcellstochemotherapy AT hansmrodermond erstressinduceddifferentiationsensitizescoloncancerstemcellstochemotherapy AT jamescpaton erstressinduceddifferentiationsensitizescoloncancerstemcellstochemotherapy AT adriennewpaton erstressinduceddifferentiationsensitizescoloncancerstemcellstochemotherapy AT louisvermeulen erstressinduceddifferentiationsensitizescoloncancerstemcellstochemotherapy AT janpaulmedema erstressinduceddifferentiationsensitizescoloncancerstemcellstochemotherapy AT gijsrvandenbrink erstressinduceddifferentiationsensitizescoloncancerstemcellstochemotherapy |
_version_ |
1725805179125628928 |