Independent phenotypic plasticity axes define mammalian metabolic and obesity sub-types
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA847415 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19593112_1.fastq.gz | Fastqsanger.gz | |||
| SRR19593112_2.fastq.gz | Fastqsanger.gz | |||
| SRR19593113_1.fastq.gz | Fastqsanger.gz | |||
| SRR19593113_2.fastq.gz | Fastqsanger.gz | |||
| SRR19593114_1.fastq.gz | Fastqsanger.gz |
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Project description:Independent phenotypic plasticity axes define mammalian metabolic and obesity sub-types [RNA-seq, mouse]
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Project 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. The clonal derivative of the CA1 OSCC cell line termed 18 here (otherwise termed pEMT-P) was treated with 0.5ng/ml TGFbeta and/or 5uM RA for eight days, with media changed every second day. The LM OSCC cell line was FACS sorted to recover the CD44highEpCAMlowCD24+ sub-population, which was then treated with 0.5ng/ml TGFbeta and/or 5uM RA for eight days, with media changed every second day. The parental CA1 and LM cell lines are included as reference samples.
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