Epigenetic profiling of EMT in pancreatic cancer cells (ChIP-seq)
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ABSTRACT:
PROVIDER: PRJNA565773 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Epigenetic profiling of EMT in pancreatic cancer cells
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Project description:<p>The involvement of membrane-bound solute carriers (SLCs) in neoplastic transdifferentiation processes is poorly defined. Here, we examined changes in the SLC landscape during epithelial-mesenchymal transition (EMT) of pancreatic cancer cells. We show that two SLCs from the organic anion/cation transporter family, SLC22A10 and SLC22A15, favor EMT via interferon (IFN) α and γ signaling activation of receptor tyrosine kinase-like orphan receptor 1 (ROR1) expression. In addition, SLC22A10 and SLC22A15 allow tumor cell accumulation of glutathione to support EMT via the IFNα/γ-ROR1 axis. Moreover, a pan-SLC22A inhibitor lesinurad reduces EMT-induced metastasis and gemcitabine chemoresistance to prolong survival in mouse models of pancreatic cancer, thus identifying new vulnerabilities for human PDAC.</p>
2021-10-15 | MTBLS1925 | MetaboLights
Project description:Epithelial plasticity – reversible modulation of a cell’s epithelial and mesenchymal features – is associated with cancer metastasis and chemoresistance. This process is classically driven by a small cohort of transcription factors, several of which have been reported to functionally interact with epigenetic modifiers at the promoters of key epithelial and mesenchymal genes. However, the extent to which epigenetic changes underlie epithelial plasticity at the genomic level remains largely unknown. Here we show that genome-wide regulation of a single histone mark, H3K36me2, is critical for establishing stable epithelial-mesenchymal states in various genetic, chemical, and cellular contexts. Through targeted CRISPR-Cas9 screening, we discovered two histone-modifying enzymes involved in the writing and erasing of H3K36me2 that act reciprocally to regulate epithelial-mesenchymal identity, tumor differentiation, and metastasis. Using genetic approaches to inhibit H3K36me2, we found that modulation of the mark itself is a conserved mechanism underlying the mesenchymal state. Although H3K36me2 is distributed broadly throughout the genome, it is associated with altered enhancer activity affecting a relatively small number of genes, including those associated with master epithelial-mesenchymal regulatory factors. Our results thus outline an epigenome-scale mechanism by which a specific histone modification regulates cellular plasticity in cancer.
2020-03-13 | GSE137521 | GEO
Project description:During pancreatic cancer progression, heterogeneous subclonal populations evolve in the primary tumor that possess differing capacities to metastasize and cause patient death. However, the genetics of metastasis reflects that of the primary tumor, and PDAC driver mutations arise early. This raises the possibility than an epigenetic process could be operative late. Using an exceptional resource of paired patient samples, we found that different metastatic subclones from the same patient possessed remarkably divergent malignant properties and global epigenetic programs. Global reprogramming was targeted to thousands of large chromatin domains across the genome that collectively specified malignant divergence. This was maintained by a metabolic shift within the pentose phosphate pathway, independent of KRAS driver mutations. Analysis of paired primary and metastatic tumors from multiple patients uncovered substantial epigenetic heterogeneity in primary tumors, which resolved into a terminally reprogrammed state in metastatic lesions. This supports a model whereby driver mutations accumulate early to initiate pancreatic tumorigenesis, followed by a period of subclonal evolution that generates sufficient intra-tumor heterogeneity for selection of epigenetic programs that may increase fitness during malignant progression and metastatic spread. To map the epigenomic landscape of pancreatic cancer progression as it evolves within patients. Chip-Seq (K27Me3, K36Me3, K9Me2/3, K4Me3 and K27Ac) of 2 patients (A13 and A38) and HPDE cell line. Patient A38 included local peritoneal metastasis and 2 distant metastsis (liver and lung mets), and 6AN treated and DMSO samples for lung matastasis. Patient A13 included 2 primary tumors and 1 distant lung metastasis. Each sample has been done with replicates.
2016-10-24 | E-GEOD-63125 | biostudies-arrayexpress
Project description:Gene expression profiling has uncovered the transcription factor Sox4 with up-regulated activity during TGFβ-induced EMT in normal and cancerous breast epithelial cells. Sox4 is indispensable for EMT and cell survival in vitro and for primary tumor growth and metastasis in vivo. Among several EMT-relevant genes, Sox4 directly regulates the expression of Ezh2, encoding the Polycomb group histone methyltransferase that trimethylates histone 3 lysine 27 (H3K27me3) for gene repression. Ablation of Ezh2 expression prevents EMT, while forced expression of Ezh2 restores EMT in Sox4-deficient cells. Ezh2-mediated H3K27me3 marks associate with key EMT genes, representing an epigenetic EMT signature that predicts patient survival. Our results identify Sox4 as a master regulator of EMT by governing the expression of the epigenetic modifier Ezh2. Our Dataset comprises of 12 ChIP-seq samples using chromatin from NMuMG cells which was immunoprecipitated using H3K27me3-specific antibody during TGFβ-induced EMT (2ng/ml) at 6 different stages (day 0, 1, 4, 7, 10, 20).
2013-06-20 | E-GEOD-45579 | biostudies-arrayexpress
Project description:loss of Men1 in mouse pancreatic islet cells alters the epigenetic landscape of a subset of target genes. H3K4me3 ChIP-seq from either mouse pancreatic islets or mouse pancreatic islet tumors harvested at different stages.
2015-04-16 | E-GEOD-63020 | biostudies-arrayexpress
Project description:BACH1 alters the expression of EMT-related genes to promote metastasis in pancreatic cancer [ChIP-Seq]
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Project description:Epigenetic profile of tissues is reprogrammed under diseased conditions. H3K4Me3 and H3K27Me3 represent active and repressive epigenetic marks, respectively. ChIP-seq is an effective tool to study global protein-DNA interactions. To study global epigenetic differences, we used H3K4Me3 antibody to evaluate its enrichment in pancreatic acinar cells of WT and Mist1-/- mice followed by next generation sequencing. We found specific hotspots that showed differential enrichment for H3K4Me3 both in WT and Mist1-/- mice. The data show that pancreatic acinar cells are epigenetically reprogrammed under stressed cellular conditions. Global H3K4Me3 profiling of WT and Mist1-/- pancreatic acinar cells using ChIP-seq.
2014-07-21 | E-GEOD-49113 | biostudies-arrayexpress