ER-Stress-Induced Differentiation Sensitizes Colon Cancer Stem Cells to Chemotherapy.

Autor:	Wielenga MCB; Tytgat Institute for Liver and Intestinal Research and Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands., Colak S; Laboratory of Experimental Oncology and Radiobiology, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands., Heijmans J; Tytgat Institute for Liver and Intestinal Research and Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands., van Lidth de Jeude JF; Tytgat Institute for Liver and Intestinal Research and Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands., Rodermond HM; Laboratory of Experimental Oncology and Radiobiology, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands., Paton JC; Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, South Australia 5005, Australia., Paton AW; Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, South Australia 5005, Australia., Vermeulen L; Laboratory of Experimental Oncology and Radiobiology, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands., Medema JP; Laboratory of Experimental Oncology and Radiobiology, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands. Electronic address: j.p.medema@amc.uva.nl., van den Brink GR; Tytgat Institute for Liver and Intestinal Research and Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands. Electronic address: g.r.vandenbrink@amc.uva.nl.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2015 Oct 20; Vol. 13 (3), pp. 489-494. Date of Electronic Publication: 2015 Oct 08.
DOI:	10.1016/j.celrep.2015.09.016
Abstrakt:	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. (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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