To identify metastasis suppressor genes, which are functionally compromised in late-stage breast cancer, we compared the gene expression profiles of an established breast cancer progression cell line model and leveraged large amounts of publically available data by applying multiple bioinformatics filters. Here we report the identification of serum deprivation response (SDPR, also known as cavin-2) as a bona fide metastasis suppressor, capable of impairing the metastatic growth of cancer cells while having no effect on the growth of primary tumors.
SDPR functions as a metastasis suppressor in breast cancer by promoting apoptosis.
Disease, Disease stage, Cell line
View SamplesIL13R2 overexpression promotes metastasis of basal-like breast cancers
Targeting IL13Ralpha2 activates STAT6-TP63 pathway to suppress breast cancer lung metastasis.
Specimen part, Cell line, Treatment
View SamplesBasal-like breast cancer (BLBC) cells share phenotypic similarities with cancer stem cells (CSCs) but the underlying molecular basis for this connection remains elusive. We hypothesized that BLBC cells are able to establish a niche permissive to the maintenance of CSCs and found that tumor cell-derived periostin (POSTN), a component of the extracellular matrix, as well as a corresponding cognate receptor, integrin v3, are highly expressed in a subset of BLBC cell lines as well as in cancer stem cell-enriched populations. Furthermore, we demonstrated that an intact periostin-integrin 3 signaling axis is required for the maintenance of breast CSCs. POSTN activates the ERK signaling pathway and regulates NF-B-mediated transcription of key cytokines, namely IL6 and IL8, which in turn mediate downstream activation of STAT3. In summary, these findings suggest that BLBC cells have an innate ability to establish a microenvironmental niche supportive of CSCs.
Tumor Cell-Derived Periostin Regulates Cytokines That Maintain Breast Cancer Stem Cells.
Cell line
View SamplesIn this study, we took advantage of a previously established breast cancer progression cell line model system, which consists of a parental MCF10A (MI) spontaneously immortalized mammary epithelial cell line and two of its derivatives: 1) MCF10ATk.cl2 (MII), a MCF10A H-Ras transformed cell line and 3) MCF10CA1h (MIII), derived from a xenograft of the MII cells in nude mice that progressed to carcinoma (1, 2). These cell lines were previously reported to exhibit distinct tumorigenic properties when re-implanted in nude mice; MI is non-tumorigenic, MII forms benign hyperplastic lesions and MIII forms low-grade, well differentiated carcinomas (2, 3). The advantage of this system is that these cell lines were derived from a common genetic background (MCF10A) and accumulated distinct genetic/epigenetic alterations in vivo enabling them to acquire a range of non-tumorigenic to carcinogenic properties. Our initial studies showed that MIII cells, but not MI or MII, exhibit an EMT phenotype, promoter DNA hypermethylation of epithelial genes and highly invasive properties in vitro.
Smad signaling is required to maintain epigenetic silencing during breast cancer progression.
Cell line
View SamplesWe have ablated TAF10 in the erythroid compartment only by crossing the TAF10lox mice with the EpoR-Cre mice and we have studied the development of the erythroid cells in vivo. TAF10 ablation led to embryonic death at E13.5 while at E12.5 there was a clear developmental defect which was reflected in the transcriptional profile of the fetal liver cells. Gata1-target genes were mostly affected and were responsible for the lethal phenotype. Overall design: mRNA from E12.5 fetal livers of TAF10lox/KO:EpoR-Cre+/- (TAF10KO) mice, TAF10HET and WT mice was profiled by NGS (Illumina).
TAF10 Interacts with the GATA1 Transcription Factor and Controls Mouse Erythropoiesis.
No sample metadata fields
View SamplesRNA editing is a mutational mechanism that specifically alters the nucleotide content in sets of transcripts while leaving their cognate genomic blueprint intact. Editing has been detected from bulk RNA-seq data in thousands of distinct transcripts, but apparent editing rates can vary widely (from under 1% to almost 100%). These observed editing rates could result from approximately equal rates of editing within each individual cell in the bulk sample, or alternatively, editing estimates from a population of cells could reflect an average of distinct, biologically significant editing signatures that vary substantially between individual cells in the population. To distinguish between these two possibilities we have constructed a hierarchical Bayesian model which quantifies the variance of editing rates at specific sites using RNA-seq data from both single cells and a cognate bulk sample consisting of ~ 106 cells. The model was applied to data from murine bone-marrow derived macrophages and dendritic cells, and predicted high variance for specific edited sites in both cell types tested. We then 1 validated these predictions using targeted amplification of specific editable transcripts from individual macrophages. Our data demonstrate substantial variance in editing signatures between single cells, supporting the notion that RNA editing generates diversity within cellular populations. Such editing-mediated RNA-level sequence diversity could contribute to the functional heterogeneity apparent in cells of the innate immune system. Overall design: 26 samples were subjected to RNA-seq: 24 single WT macrophages, and 2 bulk samples (Apobec1 WT and KO macrophages), consisting of 500,000-1 million cells each.
RNA editing generates cellular subsets with diverse sequence within populations.
Specimen part, Cell line, Subject
View SamplesThe metabolic syndrome (MetS) is characterized by the presence of metabolic abnormalities that include abdominal obesity, dyslipidemia, hypertension, increased blood glucose/insulin resistance, hypertriglyceridemia and increased risk for cardiovascular disease (CVD). The ApoE*3Leiden.human Cholesteryl Ester Transfer Protein (ApoE3L.CETP) mouse model manifests several features of the MetS upon high fat diet (HFD) feeding. Moreover, the physiological changes in the white adipose tissue (WAT) contribute to MetS comorbidities. The aim of this study was to identify transcriptomic signatures in the gonadal WAT of ApoE3L.CETP mice in discrete stages of diet-induced MetS.
Transcriptome analysis of the adipose tissue in a mouse model of metabolic syndrome identifies gene signatures related to disease pathogenesis.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Brain Endothelial- and Epithelial-Specific Interferon Receptor Chain 1 Drives Virus-Induced Sickness Behavior and Cognitive Impairment.
Sex, Specimen part, Treatment, Time
View SamplesVSV-M2 is recognized by cytosolic RIG-I. Notably, 5'-triphosphate RNA molecules derived from either viral RNA or from the synthetically produced 3pRNA can also induce RIG-I activation. MDA5 stimulation is achieved using complexed poly(I:C), a synthetic analog of viral dsRNA.
Brain Endothelial- and Epithelial-Specific Interferon Receptor Chain 1 Drives Virus-Induced Sickness Behavior and Cognitive Impairment.
Sex, Specimen part, Treatment, Time
View SamplesBrain endothelial cells are an essential part of the blood-brain-barrier (BBB) and, as such, are exposed to proinflammatory mediators as well as danger signals during infections. They might function as decisive cells mediating RNA virus- and IFN-mediated sickness behavior.
Brain Endothelial- and Epithelial-Specific Interferon Receptor Chain 1 Drives Virus-Induced Sickness Behavior and Cognitive Impairment.
Specimen part, Treatment, Time
View Samples