Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

16 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Phenotypic plasticity determines cancer stem cell therapeutic resistance in oral squamous cell carcinoma II

ABSTRACT: 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 TGFÎ² 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Adrian Biddle

PROVIDER: E-GEOD-74580 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Phenotypic plasticity determines cancer stem cell therapeutic resistance in oral squamous cell carcinoma I

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 TGFÎ² 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 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).

2016-01-12 | E-GEOD-74578 | biostudies-arrayexpress

Phenotypic plasticity determines cancer stem cell therapeutic resistance in oral squamous cell carcinoma II

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.

2016-01-12 | GSE74580 | GEO

Phenotypic plasticity determines cancer stem cell therapeutic resistance in oral squamous cell carcinoma I

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.

2016-01-12 | GSE74578 | GEO

Diverse Targets of ?-catenin during the Epithelial-Mesenchymal Transition Define Cancer Stem Cells and Predict Disease Relapse

Project description:Wnt signaling contributes to the reprogramming and maintenance of cancer stem cell (CSC) states that is activated by the epithelial-mesenchymal transition (EMT) program. However, the mechanistic relationship between the EMT and Wnt pathway in CSCs remains unclear. Chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq) indicated that EMT induces a switch from the ?-catenin/E-cadherin/Sox15 complex to the ?-catenin/Twist1/TCF4 complex, which then binds to CSC-related gene promoters. In tandem co-IP and re-ChIP experiments using epithelial-type cells, Sox15 associated with the ?-catenin/E-cadherin complex and then bound to the proximal promoter region of CASP3, consequently resulting in Twist1 cleavage and negatively regulating the ?-catenin–elicited promotion of the CSC phenotype. During the EMT, Twist1 in complex with ?-catenin enhanced ?-catenin/TCF4 transcriptional activity, which includes binding to the proximal promoter region of ABCG2, a marker of CSCs. For clinical application, the five-gene signature nuclear ?-cateninHigh/nuclear Twist1High/E-cadherinLow/Sox15Low/CD133High may be a valuable prognostic marker in patients with human lung cancer. Total cellular RNA was extracted from LM and HM20 cells after treatment with or without Wnt3a for 24hours. Human lung cancer A549 cell–derived spheres were transferred back to adhesive tissue culture plates (LM cells). To establish an EMT/metastasis cell model, LM cells were seeded onto Matrigel-coated Boyden chamber membranes. HM20 cells were serially selected for Matrigel invasion 20 times.

2015-04-04 | E-GEOD-67571 | biostudies-arrayexpress

Identification of oral carcinoma miRNA involved in Wnt/b-catenin signaling

Project description:MicroRNAs (miRNAs) participate in many biological processes and have emerged as key players in carcinogenesis. In order to identify changes in miRNAs specific for betelquid-associated oral squamous cell carcinoma (OSCC), we investigated the expression profiles of 858 miRNAs in a panel of 40 pairs of OSCC specimens and their matched non-tumorous epithelial counterparts. Eighty-four miRNAs were differentially expressed in the OSCC specimens compared to the matched tissue. Among these miRNAs, 19 downregulated miRNAs located in the chromosome 14q32.2 miRNA cluster region were analyzed. This miRNA cluster resides within a parentally imprinted region known to be important in development and growth. The re-expression of miR-329 and miR-410from this cluster significantly reduced OSCC cell proliferation and invasion and downregulated Wnt-7b, an activator of the Wnt/b-catenin pathway. Furthermore, the expression of those 2 miRNAs was restored by 5-aza-2′-deoxycytidine treatment and the expression levels of the 2 miRNAs were inversely correlated with the hypermethylation of the Meg-3 promoter in OSCC cells. Specifically, arecoline, a major betel nut alkaloid, reduces miR-329 and miR-410 expression. Our results thus provide a novel molecular insight into how betel quid may contribute to oral carcinogenesis through the epigenetic silencing of tumor suppressor miRNAs targeting the Wnt/b-catenin signaling pathway. Total RNA was obtained from 40 pairs of OSCC patients with tumor specimens and their adjacent non-tumorous epithelia.

2015-01-07 | E-GEOD-45238 | biostudies-arrayexpress

Gene expression changes in a breast cancer stem cell model.

Project description:Epithelial to mesenchymal transition (EMT) is activated during cancer invasion and metastasis, enriches for cancer stem cells (CSCs), and contributes to therapeutic resistance and disease recurrence. The epithelial cell line MCF7, can be induced to undergo EMT with the induction of PKC by PMA. 5-10% of the resulting cells have a CSC phenotype. This study looks at the transcriptome of these cells and how it differs from cells with a non-CSC phenotype. Epithelial to mesenchymal transition (EMT) is activated during cancer invasion and metastasis, enriches for cancer stem cells (CSCs), and contributes to therapeutic resistance and disease recurrence. The epithelial cell line MCF7, can be induced to undergo EMT with the induction of PKC by PMA. 5-10% of the resulting cells have a CSC phenotype. This study looks at the transcriptome of these cells and how it differs from cells with a non-CSC phenotype. MCF7 cells were stimulated with PMA and FACS sorted. 4 samples, no replicates

2014-06-22 | E-GEOD-53266 | biostudies-arrayexpress

Axl mediates acquired resistance of head and neck cancer cells to the epidermal growth factor receptor inhibitor erlotinib

Project description:Elevated expression and activity of the epidermal growth factor receptor (EGFR) is associated with development and progression of head and neck cancer (HNC) and a poor prognosis. Clinical trials with EGFR tyrosine kinase inhibitors (TKIs; eg. erlotinib) have been disappointing in HNC. To investigate the mechanisms mediating resistance to these agents, we developed a HNC cell line (HN5-ER) with acquired erlotinib resistance. In contrast to parental HN5 HNC cells, HN5-ER cells exhibited an epithelial-mesenchymal (EMT) phenotype with increased migratory potential, reduced E-cadherin and epithelial-associated miRNAs, and elevated vimentin expression. Phosphorylated RTK profiling identified Axl activation in HN5-ER cells. Growth and migration of HN5-ER cells was blocked with a specific Axl inhibitor, R428, and R428 re-sensitized HN5-ER cells to erlotinib. Microarray analysis of HN5-ER cells confirmed the EMT phenotype associated with acquired erlotinib resistance, and identified activation of gene expression associated with cell migration and inflammation pathways. Moreover, increased expression and secretion of interleukin (IL)-6 and IL-8 in HN5-ER cells suggested a role for inflammatory cytokine signaling in EMT and erlotinib resistance. Expression of the tumor suppressor miR-34a was reduced in HN5-ER cells and increasing its expression abrogated Axl expression and reversed erlotinib resistance. Finally, analysis of 302 HNC patients revealed that high tumor Axl mRNA expression was associated with poorer survival (HR 1.66, p=0.007). In summary, our results identify Axl as a key mediator of acquired erlotinib resistance in HNC and suggest that therapeutic inhibition of Axl by small molecule drugs or specific miRNAs might overcome anti-EGFR therapy resistance. Differential gene expression between parental and acquired erlotinib resistant head and neck cancer cell lines of HN5.

2013-08-10 | E-GEOD-49135 | biostudies-arrayexpress

Genome wide analysis of genes expressed in early G1 phase of the cell cycle in PMCA4 wild type and PMCA4 knockout primary vascular smooth muscle cells

Project description:Husain lab cell proliferation in vitro experimental data showed a G1 arrest in PMCA4 knockout primary vascular smooth muscle cells (VSMC). This microarray documents the different gene expression profiles of PMCA4 wild type and knockout cells at the early G1 stage in serum synchronized cell populations (n=4 populations for each genotype). Serum synchronized cell populations were Hoechst labeled and flow sorted for early G1 sub-populations (PMCA4 WT n=4; PMCA4 KO n=4) and total RNA from sorted cells was used for microarray analysis.

2014-01-21 | E-GEOD-38318 | biostudies-arrayexpress

EMT-induced stemness and tumorigenicity are fueled by an oncogenic EGF/Ras pathway

Project description:Pre-EMT GIF14 cells treated with TGF-M-NM-21 Total RNA obtained from isolated GIF-14 cells from untreated and TGF-M-NM-21-treated sample

2014-02-19 | E-GEOD-44055 | biostudies-arrayexpress

Effect of nutritive conditions, adhesion and EMT on transcriptional profile of HMECs transduced by an oncogene RAS and SNAI1, SNAI2 or SNAI3

Project description:Oncogenic stress induces a global disturbance of cellular homeostasis and subsequently triggers the activation of tumour suppressor pathways. Energy capacity loss, redox state imbalance, and biosynthetic deficiency constitute the primary signals activating safeguard mechanisms, culminating in levels of stress that should not be compatible with infinite proliferative capacities of tumour initiating cells (TIC)s or cancer stem cells (CSC)s. Here, we show that the control of the glucocorticoid response by embryonic factors involved in mammary stemness5, 6 enables basal breast CSCs to not be faced with this oncogenic stress. The glucocorticoid response is thus correlated with stemness properties in basal breast cancers and is required for neoplastic transformation of mammary progenitors. This effect does not rely on hijacking tumour suppressor pathways, but on homeostatic buffering capacity. Through extensive analysis of homeostatic parameters and metabolic profiling, we show that the glucocorticoid response in mammary CSCs limits the âWarburg effectâ, the ability of an oncogene to drive glucose fermentation in the presence of oxygen. The glucocorticoid response dampens glycolytic flow and maintains respiratory capacity resulting in reduction of mitochondria energisation. This enables CSCs to sustain carbon and nitrogen flows generated via glycolysis and the tricarboxylic acid cycle (TCA), required for homeostasis and anabolism maintenance. Overall, our results reveal the role of hormonal control of metabolic reprogramming in a CSC in rendering the cell permissive to oncogenic activity. Immortalized human mammary epithelial cells (HMEC-hTERT cells) were infected with SNAIL retroviral expression constructs and an inducible form of RAS G12V. The gene expression profiles of the resulting cell lines, cultured in standard conditions, in limited nutrient supply or after plating them 16h in low-adherent (LA) conditions, were performed.

2015-12-31 | E-GEOD-56164 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data