Gene expression data of EMT-TFs overexpressing ovarian cancer cell lines
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE145553 | GEO | 2022/05/25
REPOSITORIES: GEO
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Project description:Metastasis consists of sequential steps initiated by cancer cells invading from the primary tumor site into neighboring tissues, followed by entry into the circulatory system and completed by extravasation and growth in distal organs. Circulating tumor cells, thus, encounter and adapt to multiple environmental changes during this transition. Epithelial-to-mesenchymal transition (EMT) is a developmental program that consists of loss of epithelial features concomitant with acquisition of mesenchymal features. Activation of EMT in cancer facilitates acquisition of aggressive traits and cancer invasion. EMT plasticity (EMP), the dynamic transition between multiple hybrid states in which cancer cells display both epithelial and mesenchymal phenotypes, confers survival advantages for cancer cells in the constantly changing environment. Therefore, understanding the molecular mechanisms regulating intermediate phenotypic states along the E–M spectrum is critical. Core EMT transcription factors (EMT-TFs), ZEB, SNAI and TWIST families, play an important role in EMT and its plasticity. In the present study we characterize FLASH as a regulator of EMP and multiple EMT-TFs. We demonstrate that loss of FLASH gives rise to a hybrid E/M phenotype with high epithelial scores even in the presence of TGFβ, as determined by computational methods using expression of predetermined sets of epithelial and mesenchymal genes. We demonstrate that FLASH is regulating expression of multiple cell junction proteins with an established role in cancer progression and that its role in EMT is independent of its histone biogenesis role. Further, we show that FLASH expression in cancer lines is inversely correlated with the epithelial score, consistent with its function as a repressor of the epithelial phenotype. Nonetheless, activation of a distinct set of mesenchymal markers concomitant with epithelial markers reveals the complex role of FLASH in EMT and indicates that intermediate E/M states could arise from opposing control by FLASH on different families of EMT-TFs.
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Project description:Gene expression data of EMT-TFs overexpressing ovarian cancer cell lines
| PRJNA607542 | ENA
Project description:Ovarian cancer (OC) cells exhibit varying extents of epithelial/mesenchymal phenotype, forming an EMT spectrum based on their EMT scores. Combining 450K DNA methylation array, ChIP-sequencing of five histone H3 marks (H3K4me1, H3K4me3, H3K27Ac, H3K27me3 and H3K9me3) and transcriptomic analyses, we examined the genome-wide epigenetic profiles of OC cell lines with progressive EMT phenotypes, including a knockdown model of EMT suppressor Grainyhead-like 2 (GRHL2) which showed intermediate state transition. We identified differentially methylated CpG sites (DMCs) associated with EMT genes, found mainly at the promoters of epithelial genes including CDH1, GRHL2 and genes with GRHL2 binding sites. This prompted us to further study the epigenetic role of GRHL2. GRHL2-knockdown resulted in CpG methylation gain at GRHL2 binding sites and at DMCs associated with epithelial genes. Importantly, the changes of histone modifications occurred in GRHL2-knockdown cells are also more prominent among epithelial genes and at GRHL2 binding sites—reduction in permissive marks H3K4me3 and H3K27ac; elevated repressive mark H3K27me3—similar to the transitions observed in a four-cell-line model representing the EMT spectrum. We tested the effects of GRHL2 overexpression in conjunction with epigenetic drugs 5-azacitidine, GSK126 and mocetinostat, all of which exerted MET effects to different extents, depending on the existing cell state. Overall, GRHL2 is required for the epigenetic and chromatin remodeling of epithelial genes during EMT/MET that control intermediate phenotype switching.
2019-08-06 | GSE118407 | GEO
Project description:Ovarian cancer (OC) cells exhibit varying extents of epithelial/mesenchymal phenotype, forming an EMT spectrum based on their EMT scores. Combining 450K DNA methylation array, ChIP-sequencing of five histone H3 marks (H3K4me1, H3K4me3, H3K27Ac, H3K27me3 and H3K9me3) and transcriptomic analyses, we examined the genome-wide epigenetic profiles of OC cell lines with progressive EMT phenotypes, including a knockdown model of EMT suppressor Grainyhead-like 2 (GRHL2) which showed intermediate state transition. We identified differentially methylated CpG sites (DMCs) associated with EMT genes, found mainly at the promoters of epithelial genes including CDH1, GRHL2 and genes with GRHL2 binding sites. This prompted us to further study the epigenetic role of GRHL2. GRHL2-knockdown resulted in CpG methylation gain at GRHL2 binding sites and at DMCs associated with epithelial genes. Importantly, the changes of histone modifications occurred in GRHL2-knockdown cells are also more prominent among epithelial genes and at GRHL2 binding sites—reduction in permissive marks H3K4me3 and H3K27ac; elevated repressive mark H3K27me3—similar to the transitions observed in a four-cell-line model representing the EMT spectrum. We tested the effects of GRHL2 overexpression in conjunction with epigenetic drugs 5-azacitidine, GSK126 and mocetinostat, all of which exerted MET effects to different extents, depending on the existing cell state. Overall, GRHL2 is required for the epigenetic and chromatin remodeling of epithelial genes during EMT/MET that control intermediate phenotype switching.
2019-08-06 | GSE118406 | GEO
Project description:Ovarian cancer (OC) cells exhibit varying extents of epithelial/mesenchymal phenotype, forming an EMT spectrum based on their EMT scores. Combining 450K DNA methylation array, ChIP-sequencing of five histone H3 marks (H3K4me1, H3K4me3, H3K27Ac, H3K27me3 and H3K9me3) and transcriptomic analyses, we examined the genome-wide epigenetic profiles of OC cell lines with progressive EMT phenotypes, including a knockdown model of EMT suppressor Grainyhead-like 2 (GRHL2) which showed intermediate state transition. We identified differentially methylated CpG sites (DMCs) associated with EMT genes, found mainly at the promoters of epithelial genes including CDH1, GRHL2 and genes with GRHL2 binding sites. This prompted us to further study the epigenetic role of GRHL2. GRHL2-knockdown resulted in CpG methylation gain at GRHL2 binding sites and at DMCs associated with epithelial genes. Importantly, the changes of histone modifications occurred in GRHL2-knockdown cells are also more prominent among epithelial genes and at GRHL2 binding sites—reduction in permissive marks H3K4me3 and H3K27ac; elevated repressive mark H3K27me3—similar to the transitions observed in a four-cell-line model representing the EMT spectrum. We tested the effects of GRHL2 overexpression in conjunction with epigenetic drugs 5-azacitidine, GSK126 and mocetinostat, all of which exerted MET effects to different extents, depending on the existing cell state. Overall, GRHL2 is required for the epigenetic and chromatin remodeling of epithelial genes during EMT/MET that control intermediate phenotype switching.
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