TY  - JOUR
IS  - 7
Y1  - 2017/02/14/
A1  - Lynam-Lennon, N
A1  - Heavey, S
A1  - Sommerville, G
A1  - Bibby, BA
A1  - Ffrench, B
A1  - Quinn, J
A1  - Gasch, C
A1  - O'Leary, JJ
A1  - Gallagher, MF
A1  - Reynolds, JV
A1  - Maher, SG
N1  - Licensed under a Creative Commons Attribution 3.0 License (http://creativecommons.org/licenses/by/3.0/).
SN  - 1949-2553
ID  - discovery1534642
AV  - public
EP  - 11413
JF  - Oncotarget
N2  - Resistance to neoadjuvant chemoradiation therapy (CRT) remains a critical barrier to the effective treatment of esophageal adenocarcinoma (EAC). Cancer stem-like cells (CSCs) are a distinct subpopulation of cells implicated in the resistance of tumors to anti-cancer therapy. However, their role in the resistance of EAC to CRT is largely unknown. In this study, using a novel in vitro isogenic model of radioresistant EAC, we demonstrate that radioresistant EAC cells have enhanced tumorigenicity in vivo, increased expression of CSC-associated markers and enhanced holoclone forming ability. Further investigation identified a subpopulation of cells that are characterised by high aldehyde dehydrogenase (ALDH) activity, enhanced radioresistance and decreased expression of miR-17-5p. In vitro, miR-17-5p was demonstrated to significantly sensitise radioresistant cells to X-ray radiation and promoted the repression of genes with miR-17-5p binding sites, such as C6orf120. In vivo, miR-17-5p was significantly decreased, whilst C6orf120 was significantly increased, in pre-treatment EAC tumour samples from patients who demonstrated a poor response to neoadjuvant CRT. This study sheds novel insights into the role of CSCs in the resistance of EAC to CRT and highlights miR-17-5p as a potential biomarker of CRT sensitivity and novel therapeutic target in treatment resistant EAC.
VL  - 8
UR  - http://dx.doi.org/10.18632/oncotarget.13940
SP  - 11400
KW  - Cancer stem-like cells
KW  -  esophageal adenocarcinoma
KW  -  microRNA
KW  -  predictive biomarker
KW  -  radioresistance
TI  - MicroRNA-17 is downregulated in esophageal adenocarcinoma cancer stem-like cells and promotes a radioresistant phenotype
ER  -