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ZEB1-regulated inflammatory phenotype in breast cancer cells

ABSTRACT: ZEB1-regulated inflammatory phenotype in breast cancer cells

PROVIDER: PRJNA350678 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR4451720.fastq.gz	Fastqsanger.gz
	SRR4451721.fastq.gz	Fastqsanger.gz
	SRR4451722.fastq.gz	Fastqsanger.gz
	SRR4451717.fastq.gz	Fastqsanger.gz
	SRR4451718.fastq.gz	Fastqsanger.gz

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ZEB1-regulated inflammatory phenotype in breast cancer cells

Project description:This SuperSeries is composed of the SubSeries listed below. Zinc finger E-box binding protein 1 (ZEB1) and ZEB2 induce epithelial-mesenchymal transition (EMT) and cancer progression. However, little is known about global picture of transcriptional regulation by ZEB1 and ZEB2. Here we identified an inflammatory phenotype regulated by ZEB1 using chromatin immunoprecipitation-sequencing (ChIP-seq) and RNA-sequencing (RNA-seq) in basal type breast cancer cells, followed by gene set enrichment analysis (GSEA) of ZEB1-bound genes.

2017-06-16 | GSE89206 | GEO

ZEB1-regulated inflammatory phenotype in breast cancer cells.

Project description:Zinc finger E-box binding protein 1 (ZEB1) and ZEB2 induce epithelial-mesenchymal transition (EMT) and enhance cancer progression. However, the global view of transcriptional regulation by ZEB1 and ZEB2 is yet to be elucidated. Here, we identified a ZEB1-regulated inflammatory phenotype in breast cancer cells using chromatin immunoprecipitation sequencing and RNA sequencing, followed by gene set enrichment analysis (GSEA) of ZEB1-bound genes. Knockdown of ZEB1 and/or ZEB2 resulted in the downregulation of genes encoding inflammatory cytokines related to poor prognosis in patients with cancer, including IL6 and IL8, therefore suggesting that ZEB1 and ZEB2 have similar functions in terms of the regulation of production of inflammatory cytokines. Antibody array and ELISA experiments confirmed that ZEB1 controlled the production of the IL-6 and IL-8 proteins. The secretory proteins regulated by ZEB1 enhanced breast cancer cell proliferation and tumor growth. ZEB1 expression in breast cancer cells also affected the growth of fibroblasts in cell culture, and the accumulation of myeloid-derived suppressor cells in tumors in vivo. These findings provide insight into the role of ZEB1 in the progression of cancer, mediated by inflammatory cytokines, along with the initiation of EMT.

| S-EPMC5579340 | biostudies-literature

Zeb1-induced metabolic reprogramming of glycolysis is essential for macrophage polarization in breast cancer

Project description:Aerobic glycolysis (the Warburg effect) has been demonstrated to facilitate tumor progression by producing lactate, which has important roles as a proinflammatory and immunosuppressive mediator. However, how aerobic glycolysis is directly regulated is largely unknown. Here, we show that ectopic Zeb1 directly increases the transcriptional expression of HK2, PFKP and PKM2, which are glycolytic rate-determining enzymes, thus promoting the Warburg effect and breast cancer proliferation, migration, and chemoresistance in vitro and in vivo. In addition, Zeb1 exerts its biological effects to induce glycolytic activity in response to hypoxia via the PI3K/Akt/HIF-1α signaling axis, which contributes to fostering an immunosuppressive tumor microenvironment (TME). Mechanistically, breast cancer cells with ectopic Zeb1 expression produce lactate in the acidic tumor milieu to induce the alternatively activated macrophage M2-like phenotype through stimulation of the PKA/CREB signaling pathway. Clinically, the expression of Zeb1 is positively correlated with dysregulation of aerobic glycolysis, accumulation of M2-like tumor-associated macrophages (TAMs) and a poor prognosis in patients with breast cancer. In conclusion, these findings identify a Zeb1-dependent mechanism as a driver of breast cancer progression that acts by stimulating tumor-macrophage interplay, which could be a viable therapeutic target for the treatment of advanced human cancers.

2022-03-09 | GSE189779 | GEO

Next Generation Sequencing Facilitates Quantitative Analysis of ZEB1-Regulated Transcriptomes

Project description:The goal of this study is to analyze the transcripts regulated by ZEB1.

2017-08-10 | GSE102337 | GEO

ChIP-sequencing of ZEB1 in triple negative breast cancer cell line Hs578T

Project description:This experiment is performed to reveal the novel binding sites of ZEB1 transcription factor globally in triple negative breast cancer cell line Hs578T. We also reveal the effect of TGF cytokine on the binding sites of ZEB1.

2018-04-25 | E-MTAB-5241 | biostudies-arrayexpress

Inflammatory versus non-inflammatory breast cancers

Project description:Inflammatory versus non-inflammatory breast cancers

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ZEB1 binding sites in TGF-beta-stimulated MCF7 breast cancer cell line

Project description:We searched for roles of ZEB1 during EMT through genome-wide analysis of its binding sites in breast cancer cells.

2017-06-16 | GSE98270 | GEO

Gene expression analysis of MDA MB 231 basal type breast cancer cells with shRNA mediated control (GFP) or ZEB1 knockdown

Project description:Epithelial-to-mesenchymal transition (EMT) is a fundamental process in development and disease. If aberrantly activated it is a trigger for tumour progression and metastasis (Thiery et al 2009 Cell). It is now known that EMT activation is also associated with the maintenance of stem-cell properties (Mani et al. 2008 Cell). Since Zinc-finger enhancer binding transcription factor 1 (ZEB1) is a crucial EMT activator, we analyzed the changes in the gene expression profile that accompany shRNA mediated loss of ZEB1 in MDA MB 231 basal type breast cancer cells. MDA MB 231 is a cell line that exhibits mesenchymal characteristics, but reverts to an epithelial phenotype upon ZEB1 knock down (Spaderna et al. 2008 Cancer Research). MDA MB 231 cells were stably transfected with control (GFP) or ZEB1 shRNA. Upon puromycin selection, single cell clones were picked and characterized. Cells from two control versus two ZEB1 knockdown clones were harvested, total RNA was isolated and processed to hybridization.

2015-09-15 | E-MTAB-3482 | biostudies-arrayexpress

Identification of ZEB1-regulated gene expression changes in HCC827 human lung adenocarcinoma cells

Project description:We performed next-generation RNA sequencing for HCC827 human lung adenocarcinoma cells that are stably transfected with pcDNA3.1-ZEB1 or an empty pcDNA3.1 vector plasmid, in triplicate for each of the two HCC827 cell transfectants. The goal of this experiment is to identify putative downstream mediators of ZEB1 in human lung cancer cells. By successfully acquiring about 25 million reads for each sample, we identified more than 1,700 transcripts that are significantly regulated by ZEB1 (increased or decreased by ZEB1; p < 0.05). Among these genes, 87 of them are predicted direct targets for microRNA-200c, a well-established transcription target of ZEB1. Our results will be useful for further identification of genes that mediate the biological functions of ZEB1 in human lung cancer cells.

2016-07-12 | GSE81167 | GEO

ChIP-seq of ZEB1 in MCF7-V breast carcinoma cell line transduced with a doxycyline-inducible construct to express ZEB1

Project description:The epithelial to mesenchymal transition (EMT) is implicated in the metastatic spread of breast cancer cells. EMT transcription factors (TF) regulate different stages of EMT states. In breast cancers, estrogen receptor α (ERα) maintains the epithelial characteristics of breast tumors and is indispensable for efficient endocrine therapy. In this study we investigate whether and how ZEB1, an EMT-TF affects ERα signaling at early stages of EMT and metastasis.

2022-03-14 | GSE190095 | GEO

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