Myc activation in breast cancer is due to p53-loss and sustains self-renewal of cancer stem cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA343199 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR4250270.fastq.gz | Fastqsanger.gz | |||
| SRR4250290_1.fastq.gz | Fastqsanger.gz | |||
| SRR4250290_2.fastq.gz | Fastqsanger.gz | |||
| SRR4250300_1.fastq.gz | Fastqsanger.gz | |||
| SRR4250300_2.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 60 |
Similar Datasets
Project description:Purpose: discover the downstream pathways and the mechanism of target activation by the p53:Myc axis in normal mammary and cancer stem cells Methods: we performed ChIPseq experiments from NMuMG cells grown in adhesion under standard conditions Results: the p53:Myc axis orchestrates its transcriptional response in mammary-epithelial cells via a dual and overlapping mechanism: i) a tightly controlled epistasis driven by p53 and executed by Myc, and ii) a co-operative double occupancy of their downstream effectors at different regulatory regions
2019-01-21 | GSE87002 | GEO
Project description:Purpose: discover the downstream pathways and the mechanism of target activation by the p53:Myc axis in normal mammary and cancer stem cells Methods: we established mammosphere culture from normal and tumoral murine mammary glands and extracted RNA for expression analysis at passage 3 of the serial replating assay Results: These data demonstrate the existence of a set of 189 p53 and Myc common targets, which are implicated in the regulation of mitosis and are up-regulated in the ErbB2-tumor mammospheres, and suggest that these genes are crucial for the regulation of CSC numbers.
2019-01-21 | GSE87003 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-01-21 | GSE87004 | GEO
Project description:Wnt/b-catenin signaling is a primary pathway for stem cell maintenance during tissue renewal and a frequent target for mutations in cancer. Impaired Wnt receptor endocytosis due to loss of the ubiquitin ligase RNF43 gives rise to Wnt-hypersensitive tumors that are susceptible to anti-Wnt-based therapy. Contrary to this paradigm, we identify a class of RNF43 truncating cancer mutations that induce b-catenin-mediated transcription, despite exhibiting retained Wnt receptor downregulation. These mutations interfere with an ubiquitin-independent suppressor role of the RNF43 cytosolic tail that involves casein kinase-1 (CK1) binding and phosphorylation. Mechanistically, truncated RNF43 variants trap CK1 at the plasma membrane, thereby preventing b-catenin turnover and propelling ligandindependent target gene transcription. Gene editing of human colon stem cells shows that RNF43 truncations cooperate with p53 loss to drive a niche-independent program for self-renewal and proliferation. Moreover, these RNF43 variants confer decreased sensitivity to anti-Wnt-based therapy. Our data demonstrate the relevance of studying patient-derived mutations for understanding disease mechanisms and improved applications of precision medicine.
2020-08-14 | PXD020478 | Pride
Project description:Esrrb is a transcription factor implicated in embryonic stem (ES) cell self-renewal, yet its knockout causes intrauterine lethality due to defects in trophoblast development. Here we show that in trophoblast stem (TS) cells, Esrrb is a downstream target of fibroblast growth factor (Fgf) signalling and is critical to drive TS cell self-renewal. In contrast to its occupancy of pluripotency-associated loci in ES cells, Esrrb sustains the stemness of TS cells by direct binding and regulation of TS cell-specific transcription factors including Elf5 and Eomes. To elucidate the mechanisms whereby Esrrb controls the expression of its targets, we characterized its TS cell-specific interactome by mass spectrometry. Unlike in ES cells, Esrrb interacts in TS cells with the histone demethylase Lsd1 and with the RNA Polymerase II-associated Integrator complex. Our findings provide new insights into both, the general and context-dependent wiring of transcription factor networks in stem cells by master transcription factors.
2015-07-24 | PXD002183 | Pride
Project description:A chromatin modulator sustains self-renewal and enables differentiation of postnatal neural stem cells
| PRJNA464290 | ENA
Project description:MiRNAs have been identfied to play an important role in cancer stem cells. MiR23b is differentially expressed in various forms of cancer including colorectal cancer as compared to their normal counterparts. MiR23b regulates various aspects of cell behaviour such as differentiation, apoptosis and motility. The goal of the study was to identify the novel role of miR23b in self-renewal property of colon cancer stem cells via regulation of its candidate target mRNAs. To address this aim, HT29 colon cancer cells were transfected with miR23b Precursor, Antimir and their respective controls. RNA SEQ analysis of the cells with altered levels of miR23b assisted in the identification of interesting mRNA targets influenced by miR23b expression and involved self-renewal pathways. HT29 cells with altered levels of miR23b was subjected to RNA SEQ analysis to identify differential expresssion of mRNA targets of mIR23b
2015-02-28 | E-GEOD-59290 | biostudies-arrayexpress
Project description:p53 limits the self-renewing ability of a variety of stem cells. Here, contrary to its classical role in restraining cell proliferation, we demonstrate a divergent function of p53 in maintenance of self-renewal of the nephron progenitor population in the embryonic mouse kidney. p53-null nephron progenitor cells (NPC) exhibit progressive loss of the self-renewing progenitor niche in the cap mesenchyme, identified by Cited1 and Six2 expression, and loss of cap integrity. Nephron endowment is regulated by NPC availability and their differentiation to nephrons. Quantitatively, the Six2p53-/- cap has 30% fewer Six2GFP+ cells. While the apoptotic index is unchanged the proliferation index is significantly lower, in accordance with cell cycle analysis data showing less mutant Six2p53-/-;GFP+ cells in S and G2/M phases in comparison to Six2p53+/+;GFP+ cells. The mutant kidneys also show nephron deficit and decreased Fgf8 expression. To investigate the underlying changes in gene expression in the cap mesenchyme that contribute to the Six2p53-/- phenotype, we utilized RNA-Seq for transcriptome comparison. Top biological processes affected by p53 loss are development and morphogenesis, cell adhesion/migration, cell survival and metabolism. Cells from the mutant CM showed increased cellular ROS levels as well as deregulated expression of energy metabolism and mitochondrial genes suggesting metabolic dysfunction. Adhesion defects are visualized by decreased immunostaining of adhesion marker NCAM, and may possibly contribute to the differentiation defect as well. Altogether our data suggest a novel role for p53 in enabling self-renewal of the NPC and preservation of the progenitor niche, and thus regulating nephron endowment. mRNA profiles of wild-type (WT) and conditional p53 knockout (KO) of Six2+ mouse nephron progenitor cells (NPC) at embryonic day 15.5
2015-02-16 | E-GEOD-56253 | biostudies-arrayexpress
Project description:With their ability to self-renew and simultaneously fuel the bulk tumor mass with highly proliferative tumor cells, cancer stem cells (CSC) are supposedly driving cancer progression. However, the CSC-phenotype in colorectal cancer (CRC) is unstable and dependent on environmental cues. Since FGF2 is essential for adult and embryonic stem cell culture to maintain self-renewal, we investigated its role in advanced CRC using tumor-derived organoids as experimental model. We found that FGF-Receptor (FGFR) inhibition prevents organoid formation in very early expanding cells but induces cyst formation when applied to already established organoids. Comprehensive transcriptome analyses revealed that the induction of the transcription factor activator protein-1 (AP-1) together with a MAPK stimulation was most prominent after FGFR-inhibition. These effects resemble mechanisms of an acquired resistance against other described tyrosine kinase inhibitors such as targeted therapies against the EGF-Receptor. Furthermore, we detected elevated expression levels of several self-renewal and stemness-associated genes in organoid cultures with active FGF2 signaling. The combined data assumes that CSC are a heterogeneous subpopulation while self-renewal is a common feature regulated by many different pathways. Finally, we highlight the effects of FGF2 signaling as one of numerous aspects of the complex regulation of stemness in cancer.
2020-09-01 | GSE118949 | GEO
Project description:FGF Signaling in the Self-Renewal of Colon Cancer Organoids
| PRJNA487466 | ENA