Phenotypic Plasticity Determines Cancer Stem Cell Therapeutic Resistance in Oral Squamous Cell Carcinoma
Cancer stem cells (CSCs) drive tumour spread and therapeutic resistance, and can undergo epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) to switch between epithelial and post-EMT sub-populations. Examining oral squamous cell carcinoma (OSCC), we now show tha...
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doaj-e22f651b55d14dfab5d3551ea37742e02020-11-25T01:48:41ZengElsevierEBioMedicine2352-39642016-02-014C13814510.1016/j.ebiom.2016.01.007Phenotypic Plasticity Determines Cancer Stem Cell Therapeutic Resistance in Oral Squamous Cell CarcinomaAdrian Biddle0Luke Gammon1Xiao Liang2Daniela Elena Costea3Ian C. Mackenzie4Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UKBlizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UKThe Gade Laboratory of Pathology, Department of Clinical Medicine, University of Bergen, NorwayThe Gade Laboratory of Pathology, Department of Clinical Medicine, University of Bergen, NorwayBlizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UKCancer stem cells (CSCs) drive tumour spread and therapeutic resistance, and can undergo epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) to switch between epithelial and post-EMT sub-populations. Examining oral squamous cell carcinoma (OSCC), we now show that increased phenotypic plasticity, the ability to undergo EMT/MET, underlies increased CSC therapeutic resistance within both the epithelial and post-EMT sub-populations. The post-EMT CSCs that possess plasticity exhibit particularly enhanced therapeutic resistance and are defined by a CD44highEpCAMlow/−CD24+ cell surface marker profile. Treatment with TGFβ and retinoic acid (RA) enabled enrichment of this sub-population for therapeutic testing, through which the endoplasmic reticulum (ER) stressor and autophagy inhibitor Thapsigargin was shown to selectively target these cells. Demonstration of the link between phenotypic plasticity and therapeutic resistance, and development of an in vitro method for enrichment of a highly resistant CSC sub-population, provides an opportunity for the development of improved chemotherapeutic agents that can eliminate CSCs.http://www.sciencedirect.com/science/article/pii/S2352396416300056CancerStem cellCSCEMTPlasticityTherapyResistance |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Adrian Biddle Luke Gammon Xiao Liang Daniela Elena Costea Ian C. Mackenzie |
spellingShingle |
Adrian Biddle Luke Gammon Xiao Liang Daniela Elena Costea Ian C. Mackenzie Phenotypic Plasticity Determines Cancer Stem Cell Therapeutic Resistance in Oral Squamous Cell Carcinoma EBioMedicine Cancer Stem cell CSC EMT Plasticity Therapy Resistance |
author_facet |
Adrian Biddle Luke Gammon Xiao Liang Daniela Elena Costea Ian C. Mackenzie |
author_sort |
Adrian Biddle |
title |
Phenotypic Plasticity Determines Cancer Stem Cell Therapeutic Resistance in Oral Squamous Cell Carcinoma |
title_short |
Phenotypic Plasticity Determines Cancer Stem Cell Therapeutic Resistance in Oral Squamous Cell Carcinoma |
title_full |
Phenotypic Plasticity Determines Cancer Stem Cell Therapeutic Resistance in Oral Squamous Cell Carcinoma |
title_fullStr |
Phenotypic Plasticity Determines Cancer Stem Cell Therapeutic Resistance in Oral Squamous Cell Carcinoma |
title_full_unstemmed |
Phenotypic Plasticity Determines Cancer Stem Cell Therapeutic Resistance in Oral Squamous Cell Carcinoma |
title_sort |
phenotypic plasticity determines cancer stem cell therapeutic resistance in oral squamous cell carcinoma |
publisher |
Elsevier |
series |
EBioMedicine |
issn |
2352-3964 |
publishDate |
2016-02-01 |
description |
Cancer stem cells (CSCs) drive tumour spread and therapeutic resistance, and can undergo epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) to switch between epithelial and post-EMT sub-populations. Examining oral squamous cell carcinoma (OSCC), we now show that increased phenotypic plasticity, the ability to undergo EMT/MET, underlies increased CSC therapeutic resistance within both the epithelial and post-EMT sub-populations. The post-EMT CSCs that possess plasticity exhibit particularly enhanced therapeutic resistance and are defined by a CD44highEpCAMlow/−CD24+ cell surface marker profile. Treatment with TGFβ and retinoic acid (RA) enabled enrichment of this sub-population for therapeutic testing, through which the endoplasmic reticulum (ER) stressor and autophagy inhibitor Thapsigargin was shown to selectively target these cells. Demonstration of the link between phenotypic plasticity and therapeutic resistance, and development of an in vitro method for enrichment of a highly resistant CSC sub-population, provides an opportunity for the development of improved chemotherapeutic agents that can eliminate CSCs. |
topic |
Cancer Stem cell CSC EMT Plasticity Therapy Resistance |
url |
http://www.sciencedirect.com/science/article/pii/S2352396416300056 |
work_keys_str_mv |
AT adrianbiddle phenotypicplasticitydeterminescancerstemcelltherapeuticresistanceinoralsquamouscellcarcinoma AT lukegammon phenotypicplasticitydeterminescancerstemcelltherapeuticresistanceinoralsquamouscellcarcinoma AT xiaoliang phenotypicplasticitydeterminescancerstemcelltherapeuticresistanceinoralsquamouscellcarcinoma AT danielaelenacostea phenotypicplasticitydeterminescancerstemcelltherapeuticresistanceinoralsquamouscellcarcinoma AT iancmackenzie phenotypicplasticitydeterminescancerstemcelltherapeuticresistanceinoralsquamouscellcarcinoma |
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1725010717023666176 |