Filters
Technology
Platform
GSE83666
Homo sapiens
12 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Metabolic reprogramming is widely known as a hallmark of cancer cells to allow adaptation of cells to sustain survival signals. In the past decade, altered lipid metabolism has been recognized to be a property of malignant cells. In this report, we describe a novel oncogenic signaling pathway exclusively in tyrosine kinase inhibitor (TKI)-resistant epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). EGFR mediates TKI-resistance through regulation of the fatty acid synthase (FASN), and inhibition of this pathway using the FASN inhibitor Orlistat, triggers cell death and reduces tumor sizes both in culture systems and in vivo. Together, data shown here provide compelling evidence that the fatty acid metabolism pathway is a candidate target for TKI-resistant NSCLC treatment.
Publication Title
Fatty acid synthase mediates EGFR palmitoylation in EGFR mutated non-small cell lung cancer.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
We used microarrays to analyze the global gene expression and to identify the differentially expressed genes among wild type, prostate-specific Pten knockout, and prostate-specific Pten and Pml double knockout prostates at 12 weeks of age.
Publication Title
An aberrant SREBP-dependent lipogenic program promotes metastatic prostate cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
IlluminaHiSeq2500
Description
Cancer metabolism has been actively studied to gain insights into tumorigenic survival mechanisms and susceptibilities. In melanoma, we identify HEXIM1, a transcription elongation regulator, as a novel melanoma suppressor that participates in nucleotide stress regulation. HEXIM1 expression is low in melanoma. Its overexpression suppresses melanoma while its inactivation accelerates tumor onset in vivo. HEXIM1 responds to nucleotide stress. Knockdown of HEXIM1 rescues neural crest and melanoma nucleotide stress phenotypes in vivo. Mechanistically, under nucleotide stress, HEXIM1 is induced to form an inhibitory complex with P-TEFb, the kinase that initiates transcription elongation, to pause transcription at tumorigenic genes. The resulting alteration in gene expression also causes anti-tumorigenic transcripts to bind to and be stabilized by HEXIM1. HEXIM1 therefore plays an important role in inhibiting cancer cell-specific gene transcription while also facilitating anti-cancer gene expression. Our study reveals a novel role for HEXIM1 in coupling nucleotide metabolism with transcriptional regulation in melanoma. Overall design: RNA-seq analysis of human A375 melanoma cells treated with either DMSO or 25 µM A771726 for 0-72 hrs.
Publication Title
Stress from Nucleotide Depletion Activates the Transcriptional Regulator HEXIM1 to Suppress Melanoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2500
Description
Cancer metabolism has been actively studied to gain insights into tumorigenic survival mechanisms and susceptibilities. In melanoma, we identify HEXIM1, a transcription elongation regulator, as a novel melanoma suppressor that participates in nucleotide stress regulation. HEXIM1 expression is low in melanoma. Its overexpression suppresses melanoma while its inactivation accelerates tumor onset in vivo. HEXIM1 responds to nucleotide stress. Knockdown of HEXIM1 rescues neural crest and melanoma nucleotide stress phenotypes in vivo. Mechanistically, under nucleotide stress, HEXIM1 is induced to form an inhibitory complex with P-TEFb, the kinase that initiates transcription elongation, to pause transcription at tumorigenic genes. The resulting alteration in gene expression also causes anti-tumorigenic transcripts to bind to and be stabilized by HEXIM1. HEXIM1 therefore plays an important role in inhibiting cancer cell-specific gene transcription while also facilitating anti-cancer gene expression. Our study reveals a novel role for HEXIM1 in coupling nucleotide metabolism with transcriptional regulation in melanoma. Overall design: RNA-seq analysis of human Tet-On HEXIM1-inducible A375 melanoma cells treated with either DMSO or 1 µg/mL doxycycline in triplicate for 48 hrs.
Publication Title
Stress from Nucleotide Depletion Activates the Transcriptional Regulator HEXIM1 to Suppress Melanoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 182 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
The direct communication between our central nervous and inflammatory signalling systems is a well-recognised, yet poorly understood relationship. To increase our understanding of this relationship, we examined the metabolism of serotonin and its precursor tryptophan in macrophages under inflammatory settings. Both are involved in inflammatory signalling and known to play a major role in mood regulation. Tryptophan depletion by macrophages during inflammation can consequently result in a reduction of serotonin systemically and has been suggested to cause depression. Increased understanding of this system could help overcome the problem of treatment resistant depressed patients. To this end, we treated primary human monocyte derived macrophages with a range of anti-depressant/anti-inflammatory drugs and analysed their transcriptional profile under various inflammatory conditions. In addition to the classic endotoxic driver of inflammation, LPS, we also used IFN which is a constitutive cytokine shown to directly induce depression when administered in high doses. The anti-depressant drugs were not found to have any significant effects on macrophage inflammatory signalling. However, the anti-inflammatories drugs were found to alter components of the serotonin/tryptophan metabolism pathways. This study increases our understanding of the intricacies of immune/mood cross-talk and offers into developing anti-inflammatories as co-treatment for depression.
Publication Title
Effects of anti-inflammatory drugs on the expression of tryptophan-metabolism genes by human macrophages.
Sample Metadata Fields
Sex, Specimen part, Treatment, Subject
View Samples- Sus scrofa
- 9 Downloadable Samples
- Porcine Gene 1.1 ST Array (porgene11st)
Description
The expression was designed to determine whether exposure to CSF1-Fc has any effect on liver-specific gene expression in pigs.
Publication Title
Macrophage colony-stimulating factor (CSF1) controls monocyte production and maturation and the steady-state size of the liver in pigs.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The recent interest in the role of bone marrow derived endothelial progenitor cells in the benefits of estrogen on cardiovascular health brought us to evaluate if estrogen could affect cardiac repair more broadly by regulating biological processes involved in the functional organization of the bone marrow stem cell niche.
Publication Title
Estrogen-induced gene expression in bone marrow c-kit+ stem cells and stromal cells: identification of specific biological processes involved in the functional organization of the stem cell niche.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Canonical Wnt signaling controls proliferation and differentiation of osteogenic progenitor cells, and tumor-derived secretion of the Wnt antagonist Dickkopf-1 (Dkk1) is correlated with osteolyses and metastasis in many bone malignancies. However, the role of Dkk1 in the oncogenesis of primary osteosarcoma (OS) remains unexplored. Here, we over-expressed Dkk1 in the OS cell line MOS-J. Contrary to expectations, Dkk1 had autocrine effects on MOSJ cells in that it increased proliferation and resistance to metabolic stress in vitro. In vivo, Dkk1 expressing MOS-J cells formed larger and more destructive tumors than controls. These effects were attributed in part to up-regulation of the stress response enzyme and cancer stem cell marker aldehyde-dehydrogenase-1 (ALDH1) through Jun-N-terminal kinase signaling. This is the first report linking Dkk1 to tumor stress resistance, further supporting the targeting of Dkk1 not only to prevent and treat osteolytic bone lesions but also to reduce numbers of stress-resistant tumor cells.
Publication Title
An unexpected role for a Wnt-inhibitor: Dickkopf-1 triggers a novel cancer survival mechanism through modulation of aldehyde-dehydrogenase-1 activity.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Oryza sativa
- 11 Downloadable Samples
- Affymetrix Rice Genome Array (rice)
Description
Salt Stress response of salt-tolerant genotype FL478 compared to IR29
Publication Title
Comparing genomic expression patterns across plant species reveals highly diverged transcriptional dynamics in response to salt stress.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 32 Downloadable Samples
- Affymetrix Rat Gene 2.1 ST Array (ragene21st)
Description
We used microarray to examine changes in gene expression in the absence of Csf1r in the brain and spleen.
Publication Title
Pleiotropic Impacts of Macrophage and Microglial Deficiency on Development in Rats with Targeted Mutation of the <i>Csf1r</i> Locus.
Sample Metadata Fields
Sex
View Samples