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Genome-wide characterization of platinum persister ovarian cancer (OC) cells with upregulation of Wnt pathway receptor, Frizzled 7 (FZD7)

ABSTRACT: The goal of this study is to define molecular signature of platinum persister OC cells characterized by FZD7, and investigate the functional role of FZD7 relative to stemness and chemo-responsiveness.

ORGANISM(S): Homo sapiens

PROVIDER: GSE148003 | GEO | 2020/10/22

REPOSITORIES: GEO

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Genome-wide characterization of platinum persister ovarian cancer (OC) cells with upregulation of Wnt pathway receptor, Frizzled 7 (FZD7)

Project description:Genome-wide characterization of platinum persister ovarian cancer (OC) cells with upregulation of Wnt pathway receptor, Frizzled 7 (FZD7)

| PRJNA622798 | ENA

RNA-Seq of treatment response of platinum sensitive and platinum resistant ovarian cancer cells

Project description:Resistance to platinum-based chemotherapy is a clinical challenge in the treatment of ovarian cancer (OC) and limits survival. Therefore, innovative drugs against platinum-resistance are urgently needed. Our therapeutic concept is based on the conjugation of two chemotherapeutic compounds to a monotherapeutic pro-drug, which is taken up by cancer cells and cleaved into active cytostatic metabolites. Here, we explore the activity of the duplex-prodrug 5-FdU-ECyd, covalently linking 2'-deoxy-5-fluorouridine (5-FdU) and 3'-C-ethynylcytidine (ECyd), on platinum-resistant OC cells. RNA-Sequencing was used for characterization of 5-FdU-ECyd treated platinum-sensitive A2780 and isogenic platinum-resistant A2780cis.

2018-02-22 | GSE98230 | GEO

Molecular analysis of platinum-resistant and -sensitive ovarian cacner based on RNA-Seq analysis

Project description:Ovarian cancer (OC) is the leading cause of death from gynecologic malignancies. The most difficult issue in the treatment of ovarian cancer is the eventual development of platinum resistance. Accumulating studies have shown that circRNAs are abnormally aberrantly expressed in tumors and play critical roles in tumor growth, metastasis, stemness and resistance to therapy.To identify circRNAs that play crucial roles in maintaining the platinum resistance of ovarian cacner, we performed RNA-seq analysis in platinum-resistant（n=9） and -sensitive（n=10） ovarian cacner tissues. Candidate genes were identified by bioinformatic analysis and literature review.

2024-05-30 | GSE214302 | GEO

FZD7 Plays a Critical Role in Triple Negative Breast Cancer Proliferation

Project description:Breast cancer is genetically and clinically heterogeneous. Triple negative cancer (TNBC) is a subtype of breast cancer usually associated with poor outcome and lack of benefit from target therapy. A pathway analysis in a microarray study was performed using TNBC compared with non-triple negative breast cancer (non-TNBC). Overexpression of several Wnt pathway genes, such as frizzled homolog 7 (FZD7), Low density lipoprotein receptor-related protein 6 (LRP6) and transcription factor 7 (TCF7) has been observed in TNBC. Focus was given to the Wnt pathway receptor, FZD7. To validate its function, inhibition of FZD7 using FZD7shRNA was carried out. Notably decreased cell proliferation, suppressed invasiveness and colony formation in triple negative MDA-MB-231 and BT-20 cells were observed. Mechanism study indicated that these effects occurred through silencing the canonical Wnt signaling pathway, as evidenced by loss of nuclear accumulation of beta-catenin and decreased transcriptional activity of TCF7. In vivo study revealed that FZD7shRNA significantly suppressed the tumor formation in xenotransplation mice due to decrease cell proliferation. Our finding suggests that FZD7 involved canonical Wnt signaling pathway is essential for tumorigenesis of TNBC. Thus, FZD7 may be a biomarker and a potential therapeutic target for triple negative breast cancer.

2011-06-01 | GSE27447 | GEO

FZD7 Plays a Critical Role in Triple Negative Breast Cancer Proliferation

Project description:Breast cancer is genetically and clinically heterogeneous. Triple negative cancer (TNBC) is a subtype of breast cancer usually associated with poor outcome and lack of benefit from target therapy. A pathway analysis in a microarray study was performed using TNBC compared with non-triple negative breast cancer (non-TNBC). Overexpression of several Wnt pathway genes, such as frizzled homolog 7 (FZD7), Low density lipoprotein receptor-related protein 6 (LRP6) and transcription factor 7 (TCF7) has been observed in TNBC. Focus was given to the Wnt pathway receptor, FZD7. To validate its function, inhibition of FZD7 using FZD7shRNA was carried out. Notably decreased cell proliferation, suppressed invasiveness and colony formation in triple negative MDA-MB-231 and BT-20 cells were observed. Mechanism study indicated that these effects occurred through silencing the canonical Wnt signaling pathway, as evidenced by loss of nuclear accumulation of ï?¢-catenin and decreased transcriptional activity of TCF7. In vivo study revealed that FZD7shRNA significantly suppressed the tumor formation in xenotransplation mice due to decrease cell proliferation. Our finding suggests that FZD7 involved canonical Wnt signaling pathway is essential for tumorigenesis of TNBC. Thus, FZD7 may be a biomarker and a potential therapeutic target for triple negative breast cancer. 14 pretreatment non-triple negative breast tumors compare with 5 triple negative breast tumor.

2011-06-01 | E-GEOD-27447 | biostudies-arrayexpress

Platinum Genomes

Project description:Platinum Genomes

| PRJNA347414 | ENA

Differential and divergent activity of Insulin-like Growth Factor Binding Protein 6 (IGFBP6) in platinum-sensitive versus platinum-resistant high-grade serous ovarian carcinoma cell lines.

Project description:IGFBP6 is a secreted protein with a controversial role in human malignancies, being downregulated in the majority of human cancers, but upregulated in selected tumors. Ovarian carcinoma (OC) is a human malignancy characterized by IGFBP6 downregulation, even though the significance of its low expression during ovarian carcinogenesis is still poorly understood. IGFBP6 expression levels and the activation of its signaling pathway were evaluated in two matched OC cell lines derived from a high-grade serous ovarian cancer before and after platinum resistance (PEA1 and PEA2 cells,respectively). A whole genome gene expression analysis was comparatively performed in both cell lines upon IGFBP6 stimulation by Illumina technology. IGFBP6 gene expression in human OCs data were obtained from public datasets. Gene expression data from public datasets confirmed the downregulation of IGFBP6 from normal ovarian tissues to primary and metastatic OCs. The comparative analysis of platinum-sensitive (PEA1) and platinum-resistant (PEA2) cell lines showed quantitative and qualitative differences in the activation of IGFBP6 signaling. Indeed, IGFBP6 enhanced ERK1/2 phosphorylation only in PEA1 cells and induced a more evident and significant gene expression reprogramming in PEA1 compared to PEA2 cells. Furthermore, the analysis of selected genes modulated by IGFBP6 (i.e., FOS, JUN, TNF, IL6, IL8, and EGR1) showed an inverse regulation in PEA1 versus PEA2 cells, as well as selected hallmarks and IL-6 signaling were ositively regulated in PEA1, while inhibited in PEA2 cells.These data suggest that loss of IGFBP6 signaling may play a role in ovarian cancer progression, being likely associated to the development of platinum resistance.

2022-03-23 | GSE189717 | GEO

Expression data from human OC+BAP+ double positive versus OC-BAP- double negative cells

Project description:Subpopulation of circulating monocyte/macrophage lineage cells show a calcifying ability in vivo and in vitro. These cells may contribute to intimal calcification within atherosclerotic lesions and may have pathophysiological clinical and therapeutic implication in vascular disorders. Such cells express Osteocalcin (OC) and Bone Alkaline Phosphatase (BAP). We analysed the expression profile of human OC+BAP+ cells versus OC-BAP- cells

2013-05-17 | GSE47060 | GEO

Selective activation of FZD7 in human pluripotent stem cells

Project description:Human pluripotent stem cells ( (H1/WA01/NIH stem cell registry number 0043) were treated with WNT3a protein, a FZD7-specific WNT mimetic, and a GSK3 inihibitor in time series to determine genes differentially upregulated and downregulated across all conditions or within one condition only.

2020-09-18 | GSE158121 | GEO

Gene expression analysis of Mycobacterium tuberculosis high-persister (hip) mutants.

Project description:Bacterial persister cells are phenotypic variants of regular cells that are tolerant to antibiotics. High-persister (hip) mutants of Mycobacterium tuberculosis produce 10- to 1,000-fold more persister cells than the wild type strain when challenged with various antibiotics. Comparison of gene expression pattern of the hip mutants may provide clues as to the genetic mechanisms underlying persister formation. Transcriptome analysis will provide information on what differentiates M. tuberculosis hip strains from regular strains, which will be useful in the development of anti-persister therapy for persister cell eradication. Twelve independent M. tuberculosis hip mutants and the wild type strain were grown to stationary phase in duplicate. To avoid analyzing the drug effect, total RNA was extracted from the cultures prior to the addition of antibiotic for hybridization to Affymetrix microarrays. Data analysis was performed by comparing the hip mutants to the wild type control.

2014-04-07 | E-GEOD-55647 | biostudies-arrayexpress

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