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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Identification of enhancers in EMT and breast cancer stem cell formation

ABSTRACT: Epithelial-mesenchymal transition (EMT), the process whereby cells gain migratory and invasive properties characteristic of mesenchymal cells, plays a central role in embryogenesis and wound healing in a wide range of tissues. However, EMT has also been linked to the formation of cancer stem cells (CSCs). Many of the signaling pathways involved in EMT have also been implicated in CSC formation but the processes that contribute uniquely to CSC formation remain elusive. We have previously demonstrated that PKCÎ¸ activation is critical for EMT induction and concomitant CSC formation in the breast cancer luminal epithelial cell line, MCF7. To discover how PKC-induced alterations in the epigenome influence the EMT and CSC formation in MCF-7 cells and MDA-MB-231, we employed a combination of expression profiling and ChIP-sequencing of H3K4me1 and H3K27ac. 3 biological samples were analyzed with two different chromatin marks.

ORGANISM(S): Homo sapiens

SUBMITTER: Kristine Hardy

PROVIDER: E-GEOD-76732 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Identification of chromatin accessibility domains in human breast cancer stem cells.

Hardy K K Wu F F Tu W W Zafar A A Boulding T T McCuaig R R Sutton C R CR Theodoratos A A Rao S S

Nucleus (Austin, Tex.) 20160310 1

Epithelial-to-mesenchymal transition (EMT) is physiological in embryogenesis and wound healing but also associated with the formation of cancer stem cells (CSCs). Many EMT signaling pathways are implicated in CSC formation, but the precise underlying mechanisms of CSC formation remain elusive. We have previously demonstrated that PKC is critical for EMT induction and CSC formation in inducible breast EMT/CSC models. Here, we used formaldehyde-assisted isolation of regulatory elements-sequencing ...[more]

PMID: 26962893

Similar Datasets

Identification of chromatin accessibility domains in EMT and breast cancer stem cell formation.

Project description:Epithelial-mesenchymal transition (EMT), the process whereby cells gain migratory and invasive properties characteristic of mesenchymal cells, plays a central role in embryogenesis and wound healing in a wide range of tissues. However, EMT has also been linked to the formation of cancer stem cells (CSCs). Many of the signaling pathways involved in EMT have also been implicated in CSC formation but the processes that contribute uniquely to CSC formation remain elusive. We have previously demonstrated that PKCÎ¸ activation is critical for EMT induction and concomitant CSC formation in the breast cancer luminal epithelial cell line, MCF7. To discover how PKC-induced alterations in the epigenome influence the EMT and CSC formation in MCF-7 cells, we employed a combination of expression profiling and Formaldehyde Assisted Regulatory Elements (FAIRE)-sequencing in order to reveal novel links between gene expression and DNA accessibility changes after PKCÎ¸ activation. We found that, during EMT, increases in accessibility generally occurred in regions away from transcription start sites, low in CpG, enriched with chromatin marks of enhancer elements and motifs for FOX, AP1, TEAD and AP2. Increases in FOX and AP-1 motif accessibility were associated with genes that exhibited increased expression in CSC, while increased AP-2 accessibility was associated with genes that had higher expression in non-CSCs. This study revealed novel regions of DNA accessibility induced by PKC that contribute to the understanding of how epigenomic plasticity of cells undergoing EMT leads to the activation of genes that drive the CSC program. 2 biological samples were analysed with 2 biological replicates each and a mixed total input.

2016-03-10 | E-GEOD-71023 | 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

Chromatinized PKC-q directly regulates inducible genes in epithelial to mesenchymal transition and breast cancer stem cells

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. Signal transduction kinases play a pivotal role as chromatin-anchored proteins in eukaryotes. Here we report for the first time that protein kinase C-theta (PKC-q) regulates EMT by acting as a critical chromatin-anchored switch for inducible genes via TGF-M-NM-2 and the key inflammatory regulatory protein, NFkB. Chromatinized PKC-q exists as an active transcription complex and is required to establish a permissive chromatin state at signature EMT genes. Genome-wide analysis identifies a unique cohort of inducible PKC-q-sensitive genes that are directly tethered to PKC-q in the mesenchymal state. Collectively, we show that crosstalk between signaling kinases and chromatin is critical for eliciting inducible transcriptional programs that drive mesenchymal differentiation and CSC formation, providing novel mechanisms to target using epigenetic therapy in breast cancer. 2 biological samples were analysed, Immunoprecipitated and total input samples were obtained from each biological treatment. 2 Technical replicates were performed (samples from the sample lib prep were run on two different lanes).

2014-06-22 | E-GEOD-53320 | biostudies-arrayexpress

Identification of enhancers in EMT and breast cancer stem cell formation

2016-03-10 | GSE76732 | GEO

Identification of chromatin accessibility domains in EMT and breast cancer stem cell formation.

Project description:Epithelial-mesenchymal transition (EMT), the process whereby cells gain migratory and invasive properties characteristic of mesenchymal cells, plays a central role in embryogenesis and wound healing in a wide range of tissues. However, EMT has also been linked to the formation of cancer stem cells (CSCs). Many of the signaling pathways involved in EMT have also been implicated in CSC formation but the processes that contribute uniquely to CSC formation remain elusive. We have previously demonstrated that PKCθ activation is critical for EMT induction and concomitant CSC formation in the breast cancer luminal epithelial cell line, MCF7. To discover how PKC-induced alterations in the epigenome influence the EMT and CSC formation in MCF-7 cells, we employed a combination of expression profiling and Formaldehyde Assisted Regulatory Elements (FAIRE)-sequencing in order to reveal novel links between gene expression and DNA accessibility changes after PKCθ activation. We found that, during EMT, increases in accessibility generally occurred in regions away from transcription start sites, low in CpG, enriched with chromatin marks of enhancer elements and motifs for FOX, AP1, TEAD and AP2. Increases in FOX and AP-1 motif accessibility were associated with genes that exhibited increased expression in CSC, while increased AP-2 accessibility was associated with genes that had higher expression in non-CSCs. This study revealed novel regions of DNA accessibility induced by PKC that contribute to the understanding of how epigenomic plasticity of cells undergoing EMT leads to the activation of genes that drive the CSC program.

2016-03-10 | GSE71023 | GEO

The role of PKCtheta in Epithelial to Mesenchymal Transistion

2014-06-22 | E-GEOD-53267 | 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.

2014-06-22 | GSE53266 | 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 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

The molecular changes that have occurred in breast cancer cells through the introduction of the MZF-1 fragment

Project description:We used microarray gene expression analyses to search for epithelial-mesenchymal transition (EMT)-related genes that exhibited the greatest differences in expression in the MZF-1 fragment vector-transfected cells relative to the empty vector-transfected cells. Of the 22,203 genes analyzed in both cell lines, 1209 genes had a two-fold increase and 1557 genes had a two-fold decrease in Hs578T-M(S3) cells (P<0.05), and 1272 genes increased and 1494 genes decreased by a similar amount in MDA-MB-231-M(V4) cells. Combined, 821 of the same genes from both cell lines were up-regulated, and 931 of the same genes from both cell lines were down-regulated. The biological functions of these affected genes were diverse and included 11 EMT-related genes (ITGA5, SERPINE1 GNGI1, SEAP1, TIMP1, FN1, TMEFF1, SNAI2, VIM, CALD1 and MSN) which were down-regulated, and 5 MET-related genes (CDH1, TSPAN13, OCLN, KRT19 and DSP) which were up-regulated. To understand functions of MZF-1/Elk-1 heterodimers, we transfected the binding site-derived peptide to the cells to interrupt heterodimer formation, their DNA binding activity, PKCÎ± expression, cell migration and tumorigenicity were decreased, and the mesenchymal-epithelial transition (MET) was present.

2014-05-15 | E-GEOD-56306 | biostudies-arrayexpress

Regan2022 - Mechanosensitive EMT model with autocrine TGFbeta signaling

Project description:This model is an expansion of the Regan2022 - Mechanosensitive EMT model (MODEL2208050001); it includes a TGFβ signaling module and autocrine signaling in mesenchymal cells. The expanded 150-node (630 link) modular model undergoes EMT triggered by biomechanical and growth signaling crosstalk, or by TGFβ. As its predecessor, this model also reproduces the ability of the core EMT transcriptional network to maintain distinct epithelial, hybrid E/M and mesenchymal states, as well as EMT driven by mitogens such as EGF on stiff ECM. We also reproduce the observed lack of stepwise MET, in that our model's dynamics does not pass through the hybrid E/M state during MET. We show that in the absence of strong autocrine signals such as TGFβ (not included in this version), cells cannot maintain their mesenchymal state in the absence of mitogens, on softer matrices, or at high cell density. In contrast, potent autocrine signaling can stabilize the mesenchymal state in all but very dense monolayers on soft ECM. This expanded model also reproduces the inhibitory effects of TGFβ on proliferation and anoikis resistance in mesenchymal cells, as well as its ability to trigger apoptosis on soft ECM vs. EMT on stiff matrices. The model offers several experimentally testable predictions related to the effect of neighbors on partial vs. full EMT, the tug of war between mitosis and the maintenance of migratory hybrid E/M states, as well as cell cycle defects in dynamic, heterogeneous populations of epithelial, hybrid E/M and mesenchymal cells.

2023-12-13 | MODEL2208050002 | BioModels

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