ETV4 is necessary for estrogen signaling and growth in endometrial cancer cells [ATAC-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA532876 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8896970.fastq.gz | Fastqsanger.gz | |||
| SRR8896965.fastq.gz | Fastqsanger.gz | |||
| SRR8896966.fastq.gz | Fastqsanger.gz | |||
| SRR8896967.fastq.gz | Fastqsanger.gz | |||
| SRR8896968.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
Similar Datasets
Project description:Estrogen signaling through estrogen receptor alpha (ER) plays a major role in endometrial cancer risk and progression; however, the molecular mechanisms underlying ER’s regulatory role in endometrial cancer are poorly understood. In breast cancer cells, ER genomic binding is enabled by FOXA1 and GATA3, but the transcription factors that control ER genomic binding in endometrial cancer cells remain unknown. We previously identified ETV4 as a candidate factor controlling ER genomic binding in endometrial cancer cells and here we explore the functional importance of ETV4. Homozygous deletion of ETV4, using CRISPR/Cas9, led to greatly reduced ER binding at the majority of loci normally bound by ER. Consistent with the dramatic loss of ER binding, the gene expression response to estradiol was dampened for most genes. ETV4 contributes to estrogen signaling in two distinct ways; ETV4 loss impacts chromatin accessibility at some ER bound loci and impairs ER nuclear translocation. The diminished estrogen signaling upon ETV4 deletion led to decreased growth, particularly in 3D culture where hollow organoids were formed. Our results show that ETV4 plays a necessary role in estrogen signaling in endometrial cancer cells.
2019-04-23 | GSE129802 | GEO
Project description:Estrogen signaling through estrogen receptor alpha (ER) plays a major role in endometrial cancer risk and progression; however, the molecular mechanisms underlying ER’s regulatory role in endometrial cancer are poorly understood. In breast cancer cells, ER genomic binding is enabled by FOXA1 and GATA3, but the transcription factors that control ER genomic binding in endometrial cancer cells remain unknown. We previously identified ETV4 as a candidate factor controlling ER genomic binding in endometrial cancer cells and here we explore the functional importance of ETV4. Homozygous deletion of ETV4, using CRISPR/Cas9, led to greatly reduced ER binding at the majority of loci normally bound by ER. Consistent with the dramatic loss of ER binding, the gene expression response to estradiol was dampened for most genes. ETV4 contributes to estrogen signaling in two distinct ways; ETV4 loss impacts chromatin accessibility at some ER bound loci and impairs ER nuclear translocation. The diminished estrogen signaling upon ETV4 deletion led to decreased growth, particularly in 3D culture where hollow organoids were formed. Our results show that ETV4 plays a necessary role in estrogen signaling in endometrial cancer cells.
2019-04-23 | GSE129804 | GEO
Project description:Estrogen signaling through estrogen receptor alpha (ER) plays a major role in endometrial cancer risk and progression; however, the molecular mechanisms underlying ER’s regulatory role in endometrial cancer are poorly understood. In breast cancer cells, ER genomic binding is enabled by FOXA1 and GATA3, but the transcription factors that control ER genomic binding in endometrial cancer cells remain unknown. We previously identified ETV4 as a candidate factor controlling ER genomic binding in endometrial cancer cells and here we explore the functional importance of ETV4. Homozygous deletion of ETV4, using CRISPR/Cas9, led to greatly reduced ER binding at the majority of loci normally bound by ER. Consistent with the dramatic loss of ER binding, the gene expression response to estradiol was dampened for most genes. ETV4 contributes to estrogen signaling in two distinct ways; ETV4 loss impacts chromatin accessibility at some ER bound loci and impairs ER nuclear translocation. The diminished estrogen signaling upon ETV4 deletion led to decreased growth, particularly in 3D culture where hollow organoids were formed. Our results show that ETV4 plays a necessary role in estrogen signaling in endometrial cancer cells.
2019-04-23 | GSE129803 | GEO
Project description:ETV4 is necessary for estrogen signaling and growth in endometrial cancer cells
| PRJNA532873 | ENA
Project description:ETV4 is necessary for estrogen signaling and growth in endometrial cancer cells [ChIP-seq]
| PRJNA532875 | ENA
Project description:ETV4 is necessary for estrogen signaling and growth in endometrial cancer cells [RNA-seq]
| PRJNA532874 | ENA
Project description:Estrogen signaling through estrogen receptor alpha (ER) plays a major role in endometrial cancer risk and progression, however, the molecular mechanisms underlying ER's regulatory role in endometrial cancer are poorly understood. In breast cancer cells, ER genomic binding is enabled by FOXA1 and GATA3, but the transcription factors that control ER genomic binding in endometrial cancer cells remain unknown. We previously identified ETV4 as a candidate factor controlling ER genomic binding in endometrial cancer cells, and here we explore the functional importance of ETV4. Homozygous deletion of ETV4, using CRISPR/Cas9, led to greatly reduced ER binding at the majority of loci normally bound by ER. Consistent with the dramatic loss of ER binding, the gene expression response to estradiol was dampened for most genes. ETV4 contributes to estrogen signaling in two distinct ways. ETV4 loss affects chromatin accessibility at some ER bound loci and impairs ER nuclear translocation. The diminished estrogen signaling upon ETV4 deletion led to decreased growth, particularly in 3D culture, where hollow organoids were formed and in vivo in the context of estrogen-dependent growth. These results show that ETV4 plays an important role in estrogen signaling in endometrial cancer cells. SIGNIFICANCE: Estrogen receptor alpha (ER) is a key oncogene in endometrial cancer. This study uncovers ETV4 as an important factor in controlling the activity of ER and the growth of endometrial cancer cells. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/6/1234/F1.large.jpg.
| S-EPMC7073291 | biostudies-literature
Project description:Estrogen receptor alpha (ESR1) mutations have been identified in hormone therapy resistant breast cancer and primary endometrial cancer. Analyses in breast cancer suggests that mutant ESR1 exhibits estrogen independent activity. In endometrial cancer, ESR1 mutations are associated with worse outcomes and less obesity, however experimental investigation of these mutations has not been performed. Using a unique CRISPR/Cas9 strategy, we introduced the D538G mutation, a common endometrial cancer mutation that alters the ligand binding domain of ESR1, while epitope tagging the endogenous locus. We discovered estrogen-independent mutant ESR1 genomic binding that is significantly altered from wildtype ESR1. The D538G mutation impacted expression, including a large set of non-estrogen regulated genes, and chromatin accessibility, with most affected loci bound by mutant ESR1. Mutant ESR1 is unique from constitutive ESR1 activity as mutant-specific changes are not recapitulated with prolonged estrogen exposure. Overall, D538G mutant ESR1 confers estrogen-independent activity while causing additional regulatory changes in endometrial cancer cells that are distinct from breast cancer cells.
2019-06-11 | GSE132424 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-04-23 | GSE129805 | GEO
Project description:Estrogen receptor alpha (ESR1) mutations have been identified in hormone therapy resistant breast cancer and primary endometrial cancer. Analyses in breast cancer suggests that mutant ESR1 exhibits estrogen independent activity. In endometrial cancer, ESR1 mutations are associated with worse outcomes and less obesity, however experimental investigation of these mutations has not been performed. Using a unique CRISPR/Cas9 strategy, we introduced the D538G mutation, a common endometrial cancer mutation that alters the ligand binding domain of ESR1, while epitope tagging the endogenous locus. We discovered estrogen-independent mutant ESR1 genomic binding that is significantly altered from wildtype ESR1. The D538G mutation impacted expression, including a large set of non-estrogen regulated genes, and chromatin accessibility, with most affected loci bound by mutant ESR1. Mutant ESR1 is unique from constitutive ESR1 activity as mutant-specific changes are not recapitulated with prolonged estrogen exposure. Overall, D538G mutant ESR1 confers estrogen-independent activity while causing additional regulatory changes in endometrial cancer cells that are distinct from breast cancer cells.
2019-06-11 | GSE132428 | GEO