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SRP093883
Homo sapiens
36 Downloadable Samples
Description
The T lymphoma invasion and metastasis inducing protein 1 (TIAM1) is a guanine nucleotide exchange factor (GEF) that activates the small GTPase RAC1 and regulates a plethora of functions such as cell proliferation, migration, apoptosis and polarity. Recently, we demonstrated that TIAM1 shuttles between the cytoplasm and nucleus. To determine the nuclear role of TIAM1, we performed RNA-seq on SW620 cells transfected either with a specific pre-validated siRNA for TIAM1 (siTIAM1) or a negative control siRNA (siNT) and generated a list of TIAM1 differentially expressed genes. GSEA revealed significant enrichment among TIAM1-regulated genes for YAP-associated molecular signature. To investigate the interplay of TIAM1 with YAP/TAZ we used RNA-seq, generated a list of YAP/TAZ differentially expressed genes from SW620 cells transfected either with specific siRNAs for YAP/TAZ or a negative control siRNA and compared it with the siTIAM1 RNA-seq dataset. Interestingly, we found that 50% of the TAZ/YAP regulated genes were also TIAM1 dependent. Overall design: mRNA profiles of control, TIAM1 or YAP/TAZ knockdown SW620 cells were generated from three independent experiments using RNA-seq
Publication Title
TIAM1 Antagonizes TAZ/YAP Both in the Destruction Complex in the Cytoplasm and in the Nucleus to Inhibit Invasion of Intestinal Epithelial Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- IlluminaHiSeq1500
Description
About 50% of human malignancies exhibit unregulated signalling through the Ras-ERK1/2 (ERK) pathway, as a consequence of activating mutations in members of Ras and Raf families. However, the quest for alternative Ras-ERK pathway-directed therapies is desirable. Upon phosphorylation ERK dimerize. We had previously demonstrated that dimerization is essential for ERK extranuclear but not nuclear signaling. Furthermore, by molecular biology approaches, we showed that specifically inhibiting ERK extranuclear component, by impeding ERK dimerization, is sufficient for curtailing tumor progression. Here, we have identified a small molecule inhibitor for ERK dimerization in vitro and in vivo that, without affecting ERK phosphorylation, prevents tumorigenesis driven by Ras-ERK pathway oncogenes, both in cellular and animal models. Importantly, this compound is unaffected by resistance-acquisition processes that hamper “classical” Ras-ERK pathway inhibitors. Thus, ERK dimerization inhibitors provide the proof of principle for two novel concepts in cancer therapy: 1) The blockade of sublocalization-specific sub-signals, rather than total signals, as a means of effectively counteracting oncogenic Ras-ERK signaling. 2) Targeting regulatory protein-protein interactions such as dimerization, rather than catalytic activities, within a signaling route, as an approach for producing effective anti-tumoral agents. Strategies aimed at preventing aberrant flux through this route remain an attractive option for therapeutic intervention in cancer. In this respect, drugs inhibiting the kinase activities of BRaf and MEK have yielded promising results. Overall design: A375p cells treated with10 µM of either DEL22379, SCH772984 or DMSO as a control for two hours. mRNA from A375p cells was extrated using RNeasy mini kit (Qiagen, Germany) according to the manufacturer''s instructions. Cells were previously treated with10 µM of either DEL22379, SCH772984 or DMSO as a control for two hours.
Publication Title
Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes.
Sample Metadata Fields
No sample metadata fields
View Samples- Escherichia coli
- 10 Downloadable Samples
Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
A fermentation strategies with phosphate feeding was applied to elongate transition inti phosphate limitation for an tryptophan overproducing E. coli strain
Publication Title
Phosphate limited fed-batch processes: impact on carbon usage and energy metabolism in Escherichia coli.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 65 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Obstructive sleep apnea (OSA) has been linked to dysregulated metabolic states and treatment of sleep apnea may improve these conditions. Subcutaneous adipose tissue is a readily samplable fat depot that plays an important role in regulating metabolism. However, neither the pathophysiologic consequences of OSA nor the effects of continuous positive airway pressure (CPAP) in altering this compartment’s molecular pathways are understood. This study aimed to systematically identify subcutaneous adipose tissue transcriptional programs modulated in OSA and in response to its effective treatment with CPAP. Two subject groups were investigated: Study Group 1 was comprised of 10 OSA and 8 controls; Study Group 2 included 24 individuals with OSA studied at baseline and following CPAP. For each subject, genome-wide gene expression measurement of subcutaneous fat was performed. Differentially activated pathways elicited by OSA (Group 1) and in response to its treatment (Group 2) were determined using network and Gene Set Enrichment Analysis (GSEA). In Group 2, treatment of OSA with CPAP improved apnea hypopnea index, daytime sleepiness, and blood pressure, but not anthropometric measures. In Group 1, GSEA revealed many up-regulated gene sets in OSA subjects, most of which were involved in immuno-inflammatory (e.g., interferon-γ signaling), transcription, and metabolic processes such as adipogenesis. Unexpectedly, CPAP therapy in Group 2 subjects was also associated with up-regulation of several immune pathways as well as cholesterol biosynthesis. Collectively, our findings demonstrate that OSA alters distinct inflammatory and metabolic programs in subcutaneous fat, but these transcriptional signatures are not reversed with short-term effective therapy.
Publication Title
Obstructive sleep apnea and CPAP therapy alter distinct transcriptional programs in subcutaneous fat tissue.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Spheroids are 3D multi-cell aggregates formed in non-addherent culture conditions. In ovarian cancer (OC), they serve as a vehicle for cancer cell dissemination in the peritoneal cavity. We investigated genes and networks upregulated in three dimensional (3D) versus two-dimensional (2D) culture conditions by Affymetrix gene expression profiling and identified ALDH1A1, a cancer stem cell marker as being upregulated in OC spheroids. Network analysis confirmed ALDH1A1 upregulation in spheroids in direct connection with elements of the -catenin pathway. A parallel increase in the expression levels of -catenin and ALDH1A1 was demonstrated in spheroids vs. monolayers an in successive spheroid generations by using OC cell liness and primary OC cells. The percentage of Aldefluor positive cells was significantly higher in spheroids vs. monolayers in IGROV1, A2780, SKOV3, and primary OC cells. B-catenin knock-down decreased ALDH1A1 expression and chromatin immunoprecipitation demonstrated that -catenin directly binds to the ALDH1A1 promoter. Both siRNA mediated -catenin knock-down and a novel ALDH1A1 small molecule enzymatic inhibitor described here for the first time, decreased the number of OC spheroids (p<0.001) and cell viability. These data strongly support the role of -catenin regulated ALDH1A1 in the maintenance of OC spheroids and of a stem cell phenotype and propose new ALDH1A1 inhibitors targeting this cell population.
Publication Title
β-Catenin-regulated ALDH1A1 is a target in ovarian cancer spheroids.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 87 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Affymetrix microarray data was generated from MCF7 breast cancer cells treated in vitro with siRNAs against 78 transcription factors and signalling molecules.
Publication Title
Cell cycle gene networks are associated with melanoma prognosis.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 49 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Affymetrix microarray data were generated from A375 melanoma cells treated in vitro with siRNAs against 45 transcription factors and signalling molecules.
Publication Title
Cell cycle gene networks are associated with melanoma prognosis.
Sample Metadata Fields
Cell line
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- NextSeq 500
Description
The goal of this study was to determine how decreased mitochondrial citrate export influences gene expression in Drosophila larvae. RNA was isolated from Drosopohila sea mutants, which exhibiti decreased mitochondrial citrate transport activity, and a genetically-matched control strain during mid-L3 development. Overall design: Larvae were collected as described in Li, H., Tennessen, J. M. Preparation of Drosophila Larval Samples for Gas Chromatography-Mass Spectrometry (GC-MS)-based Metabolomics. J. Vis. Exp. (136), e57847, doi:10.3791/57847 (2018). RNA was purified from staged mid-L3 larvae using a RNeasy Mini Kit (Qiagen). Sequencing was performed using an Illumina NextSeq500 platform with 75 bp sequencing module generating 41 bp paired-end reads. After the sequencing run, demultiplexing was performed with bcl2fastq v2.20.0.422.
Publication Title
A <i>Drosophila</i> model of combined D-2- and L-2-hydroxyglutaric aciduria reveals a mechanism linking mitochondrial citrate export with oncometabolite accumulation.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Gene expression signatures were measured in logarithmic growing cultures
Publication Title
Oncogenic BRAF regulates oxidative metabolism via PGC1α and MITF.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 23 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
Metazoans utilize a handful of highly conserved signaling pathways to create a signaling backbone that governs all stages of development, by providing spatial and temporal cues that influence gene expression. How these few signals have such a versatile developmental action is of significance to evolution, development, and disease. Their versatility likely depends upon the larger-scale network they form through integration. Such integration is exemplified by cross-talk between the Notch and the Receptor Tyrosine Kinase (RTK) pathways. We examined the transcriptional output of Notch-RTK cross-talk during Drosophila development and present in vivo data that supports a role for selected mutually-regulated genes as potentially important nodal points for signal integration. We find the complex interplay between these pathways involves their mutual regulation of numerous core components of RTK signaling in addition to targets that include components of all the major signalling pathways (TGF-, Hh, Jak/Stat, Nuclear Receptor and Wnt). Interestingly, Notch-RTK integration did not lead to general antagonism of either pathway, as is commonly believed. Instead, integration had a combinatorial effect on specific cross-regulated targets, which unexpectedly included the majority of Ras-responsive genes, suggesting Notch can specify the response to Ras activation.
Publication Title
Nodal points and complexity of Notch-Ras signal integration.
Sample Metadata Fields
No sample metadata fields
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