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GSE38912
Homo sapiens
20 Downloadable Samples
Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
Heat-Shock Factor 1 (HSF1), master regulator of the heat-shock response, facilitates malignant transformation, cancer cell survival and proliferation in model systems. The common assumption is that these effects are mediated through regulation of heat-shock protein (HSP) expression. However, the transcriptional network that HSF1 coordinates directly in malignancy and its relationship to the heat-shock response have never been defined. By comparing cells with high and low malignant potential alongside their non-transformed counterparts, we identify an HSF1-regulated transcriptional program specific to highly malignant cells and distinct from heat shock. Cancer-specific genes in this program support oncogenic processes: cell-cycle regulation, signaling, metabolism, adhesion and translation. HSP genes are integral to this program, however, even these genes are uniquely regulated in malignancy. This HSF1 cancer program is active in breast, colon and lung tumors isolated directly from human patients and is strongly associated with metastasis and death. Thus, HSF1 rewires the transcriptome in tumorigenesis, with prognostic and therapeutic implications.
Publication Title
HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
Illumina HiSeq 2000, Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Tight coordination of protein translation and HSF1 activation supports the anabolic malignant state.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
Affymetrix HT Human Genome U133A Array (hthgu133a), Illumina HiSeq 2000
Description
A unifying characteristic of aggressive cancers is a profound anabolic shift in metabolism to enable sustained proliferation and biomass expansion. The ribosome is centrally situated to sense metabolic states but whether it impacts systems that promote cellular survival is unknown. Here, through integrated chemical-genetic analyses, we find that a dominant transcriptional effect of blocking protein translation in cancer cells is complete inactivation of heat shock factor 1 (HSF1), a multifaceted transcriptional regulator of the heat-shock response and many other cellular processes essential for tumorigenesis. Translational flux through the ribosome reshapes the transcriptional landscape and links the fundamental anabolic processes of protein production and energy metabolism with HSF1 activity. Targeting this link deprives cancer cells of their energy and chaperone armamentarium thereby rendering the malignant phenotype unsustainable.
Publication Title
Tight coordination of protein translation and HSF1 activation supports the anabolic malignant state.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 76 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Pheochromocytomas are neural crest-derived tumors that arise from inherited or sporadic mutations in at least six independent genes: RET, VHL, NF1, and subunits B, C and D of succinate dehydrogenase (SDH). The proteins encoded by these multiple genes regulate distinct functions. To identify molecular interactions between the distinct pathways we performed expression profiling of a large cohort of pheochromocytomas. We show here a functional link between tumors with VHL mutations and those with disruption of the genes encoding for succinate dehydrogenase (SDH) subunits B (SDHB) and D (SDHD). A transcription profile of reduced oxidoreductase is detected in all three of these tumor types, together with an angiogenesis/hypoxia profile typical of VHL dysfunction. The oxidoreductase defect, not previously detected in VHL-null tumors, is explained by suppression of the SDHB protein, a component of mitochondrial complex II. The decrease in SDHB is also noted in tumors with SDHD mutations. Gain-of-function and loss-of-function analyses show that the link between hypoxia signals (via VHL) and mitochondrial signals (via SDH) is mediated by HIF1?. These findings explain the shared features of pheochromocytomas with VHL and SDH mutations and suggest an additional mechanism for increased HIF1? activity in tumors.
Publication Title
A HIF1alpha regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2000
Description
An unbalanced karyotype, a condition known as aneuploidy, has a profound impact on cellular physiology and is a hallmark of cancer. Determining how aneuploidy affects cells is thus critical to understanding tumorigenesis. Here we show that aneuploidy interferes with the degradation of autophagosomes within lysosomes. Mis-folded proteins that accumulate in aneuploid cells due to aneuploidy-induced proteomic changes overwhelm the lysosome with cargo, leading to the observed lysosomal degradation defects. Importantly, aneuploid cells respond to lysosomal saturation. They activate a lysosomal stress pathway that specifically increases the expression of genes needed for autophagy-mediated protein degradation. Our results reveal lysosomal saturation as a universal feature of the aneuploid state that must be overcome during tumorigenesis. Overall design: RPE-1 cells either untreated or treated with one of Reversine, Bafilomycin A1 or MG132, each condition was done in triplicate. D14-*_Control: untreated control D14-*_Rev: cells treated with 0.5uM Reversine for 24hrs and harvested 48hrs later D14-*_Baf: cells treated with 0.1uM BafA1 for 6hrs D14-*_Mg: cells treated with 1uM MG132 for 24 hrs
Publication Title
Aneuploidy-induced cellular stresses limit autophagic degradation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
- Illumina HiSeq 2500
Description
MM.1S orthotopic tumors were analyzed fro their gene expression upon tumor outgrowth. In contorl/bortezomib/elesclmol and combo treatments. Overall design: examination of three tumors for each condition.
Publication Title
Mitochondrial metabolism promotes adaptation to proteotoxic stress.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
We transiently induce the Lo19S state with a dox inducible shRNa targeting PSMD2 and explore the gene expression in the presence and absence of bortezomib Overall design: one cell type (T47D), two states (Control and Lo19S) with and without treatment with 20nM bortezomib , all in triplicates
Publication Title
Mitochondrial metabolism promotes adaptation to proteotoxic stress.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Hepatocellular carcinoma (HCC) represents a major health problem as it afflicts an increasing number of patients worldwide. Albeit most of the risk factors for HCC are known, this is a deadly syndrome with a life expectancy at the time of diagnosis of less than 1 year. Definition of the molecular principles governing the neoplastic transformation of the liver is an urgent need to facilitate the clinical management of patients, based on innovative methods to detect the disease in its early stages and on more efficient therapies. In the present study we have combined the analysis of a murine model and human samples of HCC to identify genes differentially expressed early in the process of hepatocarcinogenesis, using a microarray based approach. Expression of 190 genes was impaired in murine HCC from which 65 were further validated by low-density array RT PCR. The expression of the best 45 genes was then investigated in human samples resulting in 18 genes which expression was significantly modified in HCC. Among them, JUN, methionine adenosyltransferase 1A and 2A, phosphoglucomutase 1, and acyl CoA dehydrogenase short branched chain indicate defective cell proliferation as well as one carbon pathway, glucose and fatty acid metabolism, both in HCC and cirrhotic liver, a well known preneoplastic condition. These alterations were further confirmed in public transcriptomic datasets from other authors. In addition, vasodilator stimulated phosphoprotein, an actin-associated protein involved in cytoskeleton remodelling, was also found to be increased in the liver and serum of cirrhotic and HCC patients. In addition to revealing the impairment of central metabolic pathways for liver homeostasis, further studies may probe the potential value of the reported genes for the early detection of HCC.
Publication Title
A signature of six genes highlights defects on cell growth and specific metabolic pathways in murine and human hepatocellular carcinoma.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
Bulk RNA sequencing data from neural progenitor cells under conditions of low or high growth factor and Notch pathway activation Overall design: Cells were treated with high (20 ng/ml EGF and FGF) or low (0.5 ng/ml EGF) recombinant growth factors, with or without Notch pathway inhibitor (DAPT, 10 uM) for 12h.
Publication Title
<i>Cis-</i>activation in the Notch signaling pathway.
Sample Metadata Fields
Specimen part, Subject
View Samples