title: ER-Stress-Induced Differentiation Sensitizes Colon Cancer Stem Cells to Chemotherapy.
abstract: 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.
authors.affiliation: Tytgat Institute for Liver and Intestinal Research and Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Mattheus C B
authors.initials: MCB
authors.lastname: Wielenga
authors.affiliation: Laboratory of Experimental Oncology and Radiobiology, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Selcuk
authors.initials: S
authors.lastname: Colak
authors.affiliation: Tytgat Institute for Liver and Intestinal Research and Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Jarom
authors.initials: J
authors.lastname: Heijmans
authors.affiliation: Tytgat Institute for Liver and Intestinal Research and Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Jooske F
authors.initials: JF
authors.lastname: van Lidth de Jeude
authors.affiliation: Laboratory of Experimental Oncology and Radiobiology, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Hans M
authors.initials: HM
authors.lastname: Rodermond
authors.affiliation: Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, South Australia 5005, Australia.
authors.forename: James C
authors.initials: JC
authors.lastname: Paton
authors.affiliation: Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, South Australia 5005, Australia.
authors.forename: Adrienne W
authors.initials: AW
authors.lastname: Paton
authors.affiliation: Laboratory of Experimental Oncology and Radiobiology, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Louis
authors.initials: L
authors.lastname: Vermeulen
authors.affiliation: Laboratory of Experimental Oncology and Radiobiology, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands. Electronic address: j.p.medema@amc.uva.nl.
authors.forename: Jan Paul
authors.initials: JP
authors.lastname: Medema
authors.affiliation: 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.
authors.forename: Gijs R
authors.initials: GR
authors.lastname: van den Brink
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002454:Cell Differentiation; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress; D006801:Humans; D051379:Mice; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009944:Organoplatinum Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D000077150:Oxaliplatin; D018874:Spheroids, Cellular; D056811:Unfolded Protein Response
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin