Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Ectopic CTCFL/BORIS expression in ovarian cancer precursor cells enhances cellular motility and invasion through GALNT14 and alters CTCF chromatin occupancy

ABSTRACT: High-grade serous carcinoma (HGSC) is the most aggressive and predominant form of epithelial ovarian cancer and the leading cause of gynecological cancer death. We have previously shown that CTCFL (also known as BORIS, Brother of the Regulator of Imprinted Sites) is expressed in a large proportion of ovarian cancers, which is associated with global and promoter-specific DNA hypomethylation, advanced tumor stage, and poor prognosis. To explore its functional role in HGSC, we expressed BORIS in human fallopian tube secretory epithelial cells (FTSEC), the presumptive cell of origin for HGSC. BORIS-expressing cells exhibited increased motility and invasion, and BORIS expression was associated with alterations in several cancer-associated gene expression networks, including fatty acid metabolism, TNF signaling, cell migration, and ECM-receptor interactions. Importantly, GALNT14, a glycosyltransferase gene previously implicated in cancer cell migration and invasion, was highly induced by BORIS, and GALNT14 knockdown significantly abrogated BORIS-induced cell motility and invasion. In addition, in silico analyses provided evidence for BORIS and GALNT14 co-expression in several human cancers. Finally, ChIP-seq demonstrated that expression of BORIS in FTSEC cells was associated with de novo and enhanced binding of CTCF at hundreds of loci, many of which correlated with activation of transcription at target genes, including GALNT14. Taken together, our data indicate that BORIS may promote cell motility and invasion in HGSC via upregulation of GALNT14, and suggests BORIS as a potential therapeutic target in this malignancy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE131931 | GEO | 2019/07/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

RNA-seq analysis of doxycycline-inducible BORIS/CTCFL expression in the metastatic melanoma cell line MM057

Project description:Brother of Regulator of Imprinted Sites (BORIS) is a DNA binding protein with high similarity to CCCTC binding factor (CTCF), a multifunctional transcription factor that plays an important role in genome organization. Like CTCF, BORIS plays a role in transcriptional regulation. BORIS becomes aberrantly expressed in melanoma with a higher frequency in metastatic tumors compared to primary tumors, which indicates a role for BORIS in melanoma progression. Currently, little is known about the role of BORIS in melanoma. To gain insight into the functional role of BORIS in melanoma we established doxycycline-inducible BORIS expression in the MM057 melanoma cell line that harbors a proliferation-associated transcriptome. Next, we used RNA-seq to investigate BORIS-mediated transcriptional changes. We show that differentially expressed genes are enriched among invasion-related processes and gene signatures, indicating that BORIS expression contributes to an EMT-like switch from a proliferation to invasion-associated transcriptome. In agreement with these findings, we demonstrate that BORIS overexpression leads to reduced proliferation and increased migration and invasion. Taken together, these data indicate that expression of BORIS promotes a switch from a proliferative to invasive state at both the transcriptional and phenotypic level in melanoma cell lines.

2020-01-01 | GSE126807 | GEO

Rewiring of master transcription factor cistrome during high-grade serous ovarian cancer development

Project description:The transcription factors MECOM, PAX8, SOX17 and WT1 are candidate master regulators of high-grade serous ‘ovarian’ cancer (HGSC), yet their cooperative role in the hypothesized tissue of origin, the fallopian tube secretory epithelium (FTSEC) is unknown. We generated 26 epigenome (CUT&TAG, CUT&RUN, ATAC-seq and HiC) data sets and 24 profiles of RNA-seq transcription factor knock-down followed by RNA sequencing in FTSEC and HGSC models to define binding sites and gene sets regulated by these factors in cis and trans. This revealed that MECOM, PAX8, SOX17 and WT1 are lineage-enriched, super-enhancer associated master regulators whose cooperative DNA-binding patterns and target genes are re-wired during tumor development. All four TFs were indispensable for HGSC clonogenicity and survival but only depletion of PAX8 and WT1 impaired FTSEC cell survival. These four TFs were pharmacologically inhibited by transcriptional inhibitors only in HGSCs but not in FTSECs. Collectively, our data highlights that tumor-specific epigenetic remodeling is tightly related to MECOM, PAX8, SOX17 and WT1 activity and these transcription factors are targetable in a tumor-specific manner through transcriptional inhibitors.

2023-05-12 | GSE227779 | GEO

Rewiring of master transcription factor cistrome during high-grade serous ovarian cancer development [Hi-C]

2023-05-01 | GSE229408 | GEO

BORIS/CTCFL-mediated chromatin accessibility alterations promote a pro-invasive transcriptional signature in melanoma cells

Project description:Melanoma is the deadliest form of skin cancer, due to its tendency to metastasize early. Brother of Regulator of Imprinted Sites (BORIS), also known as CCCTC binding factor-Like (CTCFL), is a transcription regulator that becomes ectopically expressed in melanoma. We recently showed that BORIS contributes to melanoma phenotype switching by altering the gene expression program of proliferative melanoma cells in favor of a more invasive phenotype. However, how BORIS alters the transcriptome remains unclear. Here, ATAC-seq was used to study BORIS-mediated chromatin accessibility alterations in proliferative melanoma cells. Genes that gained promoter accessibility following ectopic BORIS expression, were enriched for melanoma-specific invasive genes as well as invasion-associated biological processes, while promoters of genes associated with proliferation show reduce accessibility. Integration of ATAC-Seq and RNA-Seq data demonstrates that increased chromatin accessibility is associated with transcriptional upregulation of genes involved in tumor progression processes, and the aberrant activation of oncogenic transcription factors, while reduced chromatin accessibility and downregulated genes, were associated with repressed activity of tumor suppressors. Together, these findings indicate that BORIS mediates transcriptional reprogramming in melanoma cells by altering chromatin accessibility and gene expression, shifting the cellular transcription landscape of proliferative melanoma cells towards a pro-invasive genetic signature.

2023-04-21 | GSE211800 | GEO

Gene expression profiles of 2D- and 3D-cultured fallopian tube secretory epithelial cells

Project description:Background. Fallopian tube secretory epithelial cells (FTSECs) have been implicated as a cell-of-origin for high-grade serous epithelial ovarian cancer. However, there are relatively few in vitro models of this tissue type available for use in studies of FTSEC biology and malignant transformation. In vitro three-dimensional (3D) cell culture models aim to recreate the architecture and geometry of tissues in vivo and restore the complex network of cell-cell/cell-matrix interactions that occur throughout the surface of the cell membrane. Results. We have established and characterized 3D spheroid culture models of primary FTSECs. FTSEC spheroids contain central cores of hyaline matrix surrounded by mono- or multi-layer epithelial sheets. We found that 3D culturing alters the molecular characteristics of FTSECs compared to 2D cultures of the same cells. Gene expression profiling identified more than a thousand differentially expressed genes between 3D and 2D cultures of the same FTSEC lines. Pathways significantly under-represented in 3D FTSEC cultures were associated with cell cycle progression and DNA replication. This was also reflected in the reduced proliferative indices observed in 3D spheroids stained for the proliferation marker MIB1. Comparisons with gene expression profiles of fresh fallopian tube tissues revealed that 2D FTSEC cultures clustered with follicular phase tubal epithelium, whereas 3D FTSEC cultures clustered with luteal phase samples. Conclusions. This 3D model of fallopian tube secretory epithelial cells will advance our ability to study the underlying biology and etiology of fallopian tube tissues and the pathogenesis of high-grade serous epithelial ovarian cancer. 3 primary FTSEC lines were plated in 2D, or in 3D on polyHEMA coated plates

2013-09-27 | E-GEOD-51220 | biostudies-arrayexpress

Generation of low passage high grade serous ovarian cancer cell lines from primary tumors

Project description:High grade serous ovarian cancers (HGSC) are deadly malignancies that relapse despite carboplatin chemotherapy. Many commercially ovarian cancer cell lines are not good models for HGSC. Here we demonstrate that 3 low passage cell lines derived from HGSC have similar transcriptomes to their parental bulk tumors. These cell lines recapitulated tumor characteristics of the primary cancer and had responded to therapy in the same manner as primary HGSC cells, demonstrating they are accurate models for HGSCs. mRNA profiles of low passage high grade serous tumor cell lines and their parental tumors, generated by next generation sequencing, were compared.

2015-08-01 | E-GEOD-70073 | biostudies-arrayexpress

TRAF4 promotes the malignancy of ovarian high-grade serous carcinoma by activating YAP pathway

Project description:Ovarian high-grade serous carcinoma (HGSC) accounts for the majority of deaths caused by epithelial ovarian cancer. The precise molecular changes attributable for the pathogenesis of HGSC are still largely unknown. TRAF4 has been identified to be up-regulated in some cancers. However, the association between TRAF4 and the malignancy of HGSC has not been elucidated before. In this study, we aim to explore the prognostic value and function of TRAF4 in HGSC. The results of immunohistochemistry in 174 cases of HGSC showed that high expression of TRAF4 was significantly associated with a shorter overall survival (p=0.005) and recurrence-free survival (p=0.003) in HGSC. Knock-down of TRAF4 inhibited the malignancy of ovarian cancer cells, and over-expression of TRAF4 increased cell malignancy both in vitro and in vivo. Moreover, mechanism studies demonstrated that TRAF4 promoted cell malignancy by activating YAP pathway in HGSC. In conclusion, TRAF4 could be a prognostic biomarker for HGSC and increase HGSC cell malignancy by activating YAP pathway, which may serve as a potential therapeutic target for HGSC.

2022-05-15 | GSE202840 | GEO

Expression data from ovarian cancer cell line OVCAR3 following Knockdown or Knockout of BORIS (CTCFL)

Project description:The identification of prognostic biomarkers is a priority for patients suffering from high-grade serous ovarian cancer (SOC), which accounts for >70% of ovarian cancer (OC) deaths. Meanwhile borderline ovarian cancer (BOC) is a low malignancy tumor and usually patients undergo surgery with low probabilities of recurrence. However, SOC remains the most lethal neoplasm due to the lack of biomarkers for early diagnosis and prognosis. In this regard BORIS (CTCFL), a CTCF paralog, is a promising cancer biomarker that is overexpressed and controls transcription in several cancer types, mainly in OC. Studies suggest that BORIS has an important function in OC by altering gene expression, but the effect and extent to which BORIS influences transcription in OC from a genome-wide perspective is unclear. Here we sought to identify BORIS target genes in an OC cell line (OVCAR3) with potential biomarker use in OC tumor samples. To achieve this, we performed in vitro knockout (KO) and knockdown (KD) experiments of BORIS in OVCAR3 cell line followed by expression microarrays and bioinformatics network enrichment analysis to identify relevant BORIS target genes.

2019-07-31 | GSE130163 | GEO

Generation of low passage high grade serous ovarian cancer cell lines from primary tumors

2015-08-01 | GSE70073 | GEO

Gene expression profiles of 2D- and 3D-cultured fallopian tube secretory epithelial cells

Project description:Background: Fallopian tube secretory epithelial cells (FTSECs) have been implicated as a cell-of-origin for high-grade serous epithelial ovarian cancer. However, there are relatively few in vitro models of this tissue type available for use in studies of FTSEC biology and malignant transformation. In vitro three-dimensional (3D) cell culture models aim to recreate the architecture and geometry of tissues in vivo and restore the complex network of cell-cell/cell-matrix interactions that occur throughout the surface of the cell membrane. Results: We have established and characterized 3D spheroid culture models of primary FTSECs. FTSEC spheroids contain central cores of hyaline matrix surrounded by mono- or multi-layer epithelial sheets. We found that 3D culturing alters the molecular characteristics of FTSECs compared to 2D cultures of the same cells. Gene expression profiling identified more than a thousand differentially expressed genes between 3D and 2D cultures of the same FTSEC lines. Pathways significantly under-represented in 3D FTSEC cultures were associated with cell cycle progression and DNA replication. This was also reflected in the reduced proliferative indices observed in 3D spheroids stained for the proliferation marker MIB1. Comparisons with gene expression profiles of fresh fallopian tube tissues revealed that 2D FTSEC cultures clustered with follicular phase tubal epithelium, whereas 3D FTSEC cultures clustered with luteal phase samples. Conclusions: This 3D model of fallopian tube secretory epithelial cells will advance our ability to study the underlying biology and etiology of fallopian tube tissues and the pathogenesis of high-grade serous epithelial ovarian cancer.

2013-09-27 | GSE51220 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data