Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA339558 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR4044900.fastq.gz | Fastqsanger.gz | |||
| SRR4044901.fastq.gz | Fastqsanger.gz | |||
| SRR4044902.fastq.gz | Fastqsanger.gz | |||
| SRR4044903.fastq.gz | Fastqsanger.gz | |||
| SRR4044904.fastq.gz | Fastqsanger.gz |
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Project description:Genetic and epigenetic changes in mammary epithelial cells facilitate epithelial-to-mesenchymal transition (EMT) which leads to invasion and metastasis. RUNX1 is a phenotypic transcription factor pivotal for maintenance of mammary epithelial phenotype, whose loss leads to EMT. However, the mechanisms by which RUNX1 maintains mammary epithelial phenotype are not known. Here, we report RUNX1-mediated mitotic gene bookmarking as a key epigenetic mechanism through which RUNX1 stabilizes mammary epithelial phenotype by conveying regulatory information for cell proliferation, growth, and identity through successive cell divisions. Immunofluorescence microscopy and chromatin immunoprecipitation with high throughput sequencing of asynchronous, mitotic, and G1 MCF10A breast epithelial cells revealed RUNX1 association with target genes through interphase and mitosis. RUNX1 mitotically bookmarked both RNA Pol and II transcribed genes involved in proliferation, growth, and mammary epithelial phenotype maintenance. Inhibition of RUNX1 DNA binding by a specific small molecule inhibitor led to phenotypic changes, apoptosis, and differential expression of ribosomal RNA as well as protein coding genes (e.g. HES1 and H2AFX) and long non-coding RNA (e.g. NEAT1 and MALAT1) genes involved in cellular phenotype. Together these findings reveal a novel epigenetic regulatory role of RUNX1 in normal-like breast epithelial cells and demonstrate mitotic bookmarking target genes by RUNX1 is necessary to maintain breast epithelial phenotype. Disruption of RUNX1 bookmarking by a pharmacological inhibitor results in initiation of epithelial to mesenchymal transition, an essential first step in the onset of breast cancer.
2020-07-14 | GSE121370 | GEO
Project description:The Runx1 transcription factor is essential for hematopoietic differentiation and mutations underlie various leukemias. Here we demonstrate a role for Runx1 in the MCF10 cell series model of breast cancer progression. The highest level of Runx1 that occurs in normal like mammary epithelial cells (MCF10A) is decreased in tumorigenic (MCF10AT1) and metastatic (MCF10CA1a) breast cancer cells. We show that depletion of Runx1 in MCF10A cells results in striking changes in cell morphology and induction of epithelial-mesenchymal transition (EMT) via several signaling pathways. Analyses of breast tumors and patient survival data reveal that loss of Runx1 is associated with poor prognosis and decreased survival. Re-expressing Runx1 in MCF10AT1 breast cancer cells restores the epithelial phenotype. These results identify a novel function for Runx1 in sustaining normal epithelial morphology and preventing EMT. These mechanisms suggest Runx1 levels in early stage tumors can be used as a prognostic indicator of tumor progression.
2017-04-17 | GSE85857 | GEO
Project description:We previously identified a gene signature predicted to regulate the epithelial-mesenchymal transition (EMT) in both epithelial tissue stem cells and breast cancer cells. A phenotypic RNA interference (RNAi) screen identified the genes within this 140-gene signature that promoted the conversion of mesenchymal epithelial cell adhesion molecule-negative (EpCAM-) breast cancer cells to an epithelial EpCAM+/high phenotype. The screen identified 10 of the 140 genes whose individual knockdown was sufficient to promote EpCAM and E-cadherin expression. Among these 10 genes, RNAi silencing of the SWI/SNF chromatin-remodeling factor Smarcd3/Baf60c in EpCAM- breast cancer cells gave the most robust transition from the mesenchymal to epithelial phenotype. Conversely, expression of Smarcd3/Baf60c in immortalized human mammary epithelial cells induced an EMT. The mesenchymal-like phenotype promoted by Smarcd3/Baf60c expression resulted in gene expression changes in human mammary epithelial cells similar to that of claudin-low triple-negative breast cancer cells. These mammary epithelial cells expressing Smarcd3/Baf60c had upregulated Wnt5a expression. Inhibition of Wnt5a by either RNAi knockdown or blocking antibody reversed Smarcd3/Baf60c-induced EMT. Thus, Smarcd3/Baf60c epigenetically regulates EMT by activating WNT signaling pathways. sampleXreference
2013-08-19 | E-GEOD-40145 | biostudies-arrayexpress
Project description:Epithelial to Mesenchymal Transition (EMT) has been associated with cancer cell heterogeneity, plasticity and metastasis. It has been the subject of several modeling effort. This logical model of the EMT cellular network aims to assess microenvironmental signals controlling cancer-associated phenotypes amid the EMT continuum. Its outcomes relate to the qualitative degrees of cell adhesions by adherent junctions and focal adhesions, two features affected during EMT. Model attractors recover epithelial, mesenchymal and hybrid phenotypes, and simulations show that hybrid phenotypes may arise through independent molecular paths, involving stringent extrinsic signals.
Of particular interest, model predictions and their experimental validations indicated that: 1) ECM stiffening is a prerequisite for cells overactivating FAK-SRC to upregulate SNAIL1 and acquire a mesenchymal phenotype, and 2) FAK-SRC inhibition of cell-cell contacts through the Receptor Protein Tyrosine Phosphates kappa leads to the acquisition of a full mesenchymal rather than a hybrid phenotype.
2020-06-30 | MODEL2004040001 | BioModels
Project description:We previously identified a gene signature predicted to regulate the epithelial-mesenchymal transition (EMT) in both epithelial tissue stem cells and breast cancer cells. A phenotypic RNA interference (RNAi) screen identified the genes within this 140-gene signature that promoted the conversion of mesenchymal epithelial cell adhesion molecule-negative (EpCAM-) breast cancer cells to an epithelial EpCAM+/high phenotype. The screen identified 10 of the 140 genes whose individual knockdown was sufficient to promote EpCAM and E-cadherin expression. Among these 10 genes, RNAi silencing of the SWI/SNF chromatin-remodeling factor Smarcd3/Baf60c in EpCAM- breast cancer cells gave the most robust transition from the mesenchymal to epithelial phenotype. Conversely, expression of Smarcd3/Baf60c in immortalized human mammary epithelial cells induced an EMT. The mesenchymal-like phenotype promoted by Smarcd3/Baf60c expression resulted in gene expression changes in human mammary epithelial cells similar to that of claudin-low triple-negative breast cancer cells. These mammary epithelial cells expressing Smarcd3/Baf60c had upregulated Wnt5a expression. Inhibition of Wnt5a by either RNAi knockdown or blocking antibody reversed Smarcd3/Baf60c-induced EMT. Thus, Smarcd3/Baf60c epigenetically regulates EMT by activating WNT signaling pathways.
2013-08-19 | GSE40145 | GEO
Project description:Expression data of mammary epithelial cells during the epithelial-mesenchymal transition
| PRJNA186603 | ENA
Project description:The ability of breast cancer cells to transiently transition between epithelial and mesenchymal states is critical to complete the metastatic process. In contrast, induction of epithelial-mesenchymal transition (EMT) through the acquisition of drug persistence is a more stable event. Herein, we utilize Her2 transformed human mammary epithelial (HMLE) cells to compare a reversible model of EMT induced by TGF-beta to a stable mesenchymal phenotype induced by chronic exposure to the ErbB kinase inhibitor, lapatinib. Indeed, only a TGF-beta cells capable of returning to an epithelial phenotype resulted in long bone metastasis (BM). These four cell populations were anylzed by RNA sequencing.
2019-06-04 | GSE115255 | GEO
Project description:The epithelial-mesenchymal transition (EMT) is an embryonic transdiffrentiation program which consists of the conversion of polarized epithelial cells into a motile mesenchymal phenotype. EMT is aberrantly reactivated during tumor progression, promoting metastatic dissemination. Herein, we demonstrate that EMT permissive conditions also favor tumor initiation by minimizing the number of events required for neoplastic transformation. We further demonstrated that even partial commitment of human mammary epithelial cells into an EMT program is sufficient to confer malignant properties, suggesting that the reactivation of embryonic EMT inducers participate to the primary tumor growth long before the initiation of the invasion-metastasis cascade. Human mammary epithelial cells (HMEC) were sequentially depleted in p53 through RNA interference (shp53), transduced with H-RasG12V and immortalized by hTert. Two different Tert/shp53/Ras cell population emerge that display either an epithelial (Epi) or a mesenchymal (Mes) phenotype. Gene expression profiles of the Tert/shp53 control cells and of tert/shp53/Ras/Epi and Tert/shp53/Ras/Mes were analyzed.
2012-01-31 | E-GEOD-26541 | biostudies-arrayexpress
Project description:We quantified protein expression changes between epithelial and mesechymal stages in immortalized human mammary epithelial cells (HMLE). Epithelial–mesenchymal transition is induced by expressing an EMT-TF, Twist.
2019-06-24 | PXD012001 | Pride