 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jan 12, 2016 |
| Title |
Phenotypic plasticity determines cancer stem cell therapeutic resistance in oral squamous cell carcinoma I |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
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.
|
| |
|
| Overall design |
The CA1 OSCC cell line was sub-cloned to derive 4 clonal sub-lines, termed pEMT-P, pEMT-S, Epi-S and Epi-P (here 18, 23, 7 and 4 respectively).
|
| |
|
| Contributor(s) |
Biddle A, Mackenzie IC |
| Citation(s) |
26981578 |
| |
| Submission date |
Nov 02, 2015 |
| Last update date |
Aug 13, 2018 |
| Contact name |
Adrian Biddle |
| E-mail(s) |
a.biddle@qmul.ac.uk
|
| Organization name |
Queen Mary, University of London
|
| Department |
Blizard Institute
|
| Street address |
4 Newark Street
|
| City |
London |
| ZIP/Postal code |
E1 2AT |
| Country |
United Kingdom |
| |
|
| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
|
| Samples (5)
|
|
| Relations |
| BioProject |
PRJNA300869 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE74578_RAW.tar |
26.2 Mb |
(http)(custom) |
TAR |
| GSE74578_non-normalized.txt.gz |
1.6 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...