Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA281386 | ENA |
REPOSITORIES: ENA
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Project description:Effects of a humanized CD47 antibody and SIRPα on triple negative breast carcinoma stem cells
| PRJNA1036171 | ENA
Project description:Signaling through the thrombospondin-1 receptor CD47 broadly limits cell and tissue survival of stress, but the molecular mechanisms are incompletely understood. We now show that loss of CD47 permits sustained proliferation of primary murine endothelial cells and enables these cells to spontaneously reprogram to form multipotent embryoid bodies. c-Myc, Klf4, Oct4, and Sox2 expression is elevated in CD47-null endothelial cells, in several tissues of CD47- or thrombospondin-1-null mice, and in a human T cell line lacking CD47. CD47 knockdown acutely increases mRNA levels of c-Myc and other stem cell transcription factors in cells and in vivo, whereas CD47 ligation by thrombospondin-1 suppresses c-Myc expression. The inhibitory effects of increasing CD47 levels can be overcome by maintaining c-Myc expression and are absent in cells with dysregulated c-Myc. Thus, CD47 antagonists enable cell self-renewal and reprogramming by overcoming negative regulation of c-Myc and other stem cell transcription factors. To identify gene expression changes associated with CD47 null cells, we compared the gene expression profile of these cells with WT endothelial cell, CD47 null Embryoid bodies cells and an established Embryonic Stem cell line.
2013-07-10 | E-GEOD-43133 | biostudies-arrayexpress
Project description:Signal regulatory protein alpha (SIRPα, designated CD172a), also called SHPS-1 (SHP substrate 1) binds to CD47, a receptor for Thromobospondin-1 (TSP1). To block CD47-SIRP interaction, several CD47 blocking agents are in clinical trials. The purpose of this project is to explore the effects of SIRPFc signaling on bCSCs (breast cancer stem cells) derived from MDA-MB- 231 cells, when bCSCs were treated with either SIRPFc or CD47 blocking antibody CC90002 from Celgene Corporation.
2024-02-20 | GSE247052 | GEO
Project description:Intercellular communication is critical for integrating complex signals in multicellular eukaryotes. Vascular endothelial cells and T lymphocytes closely interact during the recirculation and trans-endothelial migration of T cells. In addition to direct cell-cell contact, we show that T cell derived extracellular vesicles can interact with endothelial cells and modulate their cellular functions. Thrombospondin-1 and its receptor CD47 are expressed on exosomes/ectosomes derived from T cells, and these extracellular vesicles are internalized and modulate signaling in both T cells and endothelial cells. Extracellular vesicles released from cells expressing or lacking CD47 differentially regulate activation of T cells induced by engaging the T cell receptor. Similarly, T cell-derived extracellular vesicles modulate endothelial cell responses to vascular endothelial growth factor and tube formation in a CD47-dependent manner. Uptake of T cell derived extracellular vesicles by recipient endothelial cells globally alters gene expression in a CD47-dependent manner. CD47 also regulates the mRNA content of extracellular vesicles in a manner consistent with some of the resulting alterations in target endothelial cell gene expression. Therefore, the thrombospondin-1 receptor CD47 directly or indirectly regulates intercellular communication mediated by the transfer of extracellular vesicles between vascular cells. Treatment with B6H12 antibody inhibited co-immunoprecipitation of EGFR with CD47 and inhibited EGF-induced EGFR tyrosine phosphorylation. B6H12 treatment of bCSC also suppressed asymmetric cell division and cell proliferation and up-regulated caspase 3/7 activity. Correspondingly, caspase-7 cleavage in human breast cancers correlated with CD47 expression. Our data shows that B6H12 specifically targets bCSCs but not differentiated cancer cells, and this CD47 signaling is independent of SIRPα. Three replicates of each condition were generated. Three replicates of each MDA-231 attached cells (differentiated), MDA-231 in suspension cells (bCSC), MDA-231 in suspension cells (bCSC) treated with Control Antibody and MDA-231 in suspension cells (bCSC) treated with B6H12 Antibody.
2016-04-01 | E-GEOD-67966 | biostudies-arrayexpress
Project description:Centromere protein U (CENPU), which is a critical component of the centromere complex, is involved in the cell filament. However, limited research has been conducted on the relationship between CENPU expression and tumors. Immunohistochemical assessment of clinical samples and analysis of TCGA data revealed a positive correlation between CENPU expression and the degree of invasiveness in breast cancer cells. CENPU promoted stem-cell-like behavior and tumorigenicity and induced malignancy in breast cancer cells. Mechanistically, CENPU promoted furin activity by inhibiting its lysosomal degradation. Furin, which is a precursor-processing enzyme of nerve growth factor (NGF), promoted the conversion of proNGF to NGF which could promote breast cancer stem cells in triple-negative breast cancers. . A tumorigenesis assay conducted in a mouse model showed that CENPU promoted tumorigenesis, and treatment with a furin inhibitor suppressed this effect. Our findings revealed that CENPU plays a critical role in furin-mediated signaling responsible for tumorigenesis. Therefore, CENPU may be a novel molecular target in triple-negative breast cancer.
2025-03-08 | PXD061628 |
Project description:Triple negative breast cancers lack targeted therapies with little side effects and contain higher percentage of cancer stem cells than the other breast cancer subtypes. Genes capturing the features of cancer stem cells of such diseases may serve as potential subtyping marker or therapeutic targets for triple negative breast cancer management. This data descriptor presents a set of transcriptome data from 3 cohorts of cancer stem cells as represented as CD44+/CD24-/low and 2 cohorts of non-cancer stem cells isolated from triple negative breast cancer cells, each having 3 replicates.
2019-06-04 | GSE132083 | GEO
Project description:We previously identified a gene signature predicted to regulate the epithelial-mesenchymal transition (EMT) in both epithelial tissue stem cells and breast cancer cells. A phenotypic RNA interference (RNAi) screen identified the genes within this 140-gene signature that promoted the conversion of mesenchymal epithelial cell adhesion molecule-negative (EpCAM-) breast cancer cells to an epithelial EpCAM+/high phenotype. The screen identified 10 of the 140 genes whose individual knockdown was sufficient to promote EpCAM and E-cadherin expression. Among these 10 genes, RNAi silencing of the SWI/SNF chromatin-remodeling factor Smarcd3/Baf60c in EpCAM- breast cancer cells gave the most robust transition from the mesenchymal to epithelial phenotype. Conversely, expression of Smarcd3/Baf60c in immortalized human mammary epithelial cells induced an EMT. The mesenchymal-like phenotype promoted by Smarcd3/Baf60c expression resulted in gene expression changes in human mammary epithelial cells similar to that of claudin-low triple-negative breast cancer cells. These mammary epithelial cells expressing Smarcd3/Baf60c had upregulated Wnt5a expression. Inhibition of Wnt5a by either RNAi knockdown or blocking antibody reversed Smarcd3/Baf60c-induced EMT. Thus, Smarcd3/Baf60c epigenetically regulates EMT by activating WNT signaling pathways. sampleXreference
2013-08-19 | E-GEOD-40145 | biostudies-arrayexpress
Project description:Therapeutic strategies that improve survival outcomes for advanced-stage breast cancers have proven a major clinical challenge. Here, we define an androgen receptor signalling network that governs the maintenance and de novo formation of cancer stem cells in triple-negative breast cancer. In response to chemotherapy, androgen receptor activation switches cells into a cancer stem cell state, while androgen receptor antagonism suppresses cancer stem cell formation and function. In vivo, we validate that the androgen receptor antagonist, seviteronel, significantly improves chemotherapy-mediated inhibition of primary and metastatic tumour growth.
2023-12-03 | GSE184647 | GEO
Project description:Therapeutic strategies that improve survival outcomes for advanced-stage breast cancers have proven a major clinical challenge. Here, we define an androgen receptor signalling network that governs the maintenance and de novo formation of cancer stem cells in triple-negative breast cancer. In response to chemotherapy, androgen receptor activation switches cells into a cancer stem cell state, while androgen receptor antagonism suppresses cancer stem cell formation and function. In vivo, we validate that the androgen receptor antagonist, seviteronel, significantly improves chemotherapy-mediated inhibition of primary and metastatic tumour growth.
2023-12-03 | GSE184455 | GEO
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