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GSE27309
Mus musculus
10 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Tumor cells exhibit aberrant metabolism characterized by high glycolysis even in the presence of oxygen. This metabolic reprogramming, known as the Warburg effect, provides tumor cells with the substrates and redox potential required for the generation of biomass. Here, we show that the mitochondrial NAD-dependent deacetylase SIRT3 is a crucial regulator of the Warburg effect. SIRT3 loss promotes a metabolic profile consistent with high glycolysis required for anabolic processes in vivo and in vitro. Mechanistically, SIRT3 mediates metabolic reprogramming independently of mitochondrial oxidative metabolism and through HIF1a, a transcription factor that controls expression of key glycolytic enzymes. SIRT3 loss increases reactive oxygen species production, resulting in enhanced HIF1a stabilization. Strikingly, SIRT3 is deleted in 40% of human breast cancers, and its loss correlates with the upregulation of HIF1a target genes. Finally, we find that SIRT3 overexpression directly represses the Warburg effect in breast cancer cells. In sum, we identify SIRT3 as a regulator of HIF1a and a suppressor of the Warburg effect.
Publication Title
SIRT3 opposes reprogramming of cancer cell metabolism through HIF1α destabilization.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The Sin3 histone deacetylase (HDAC) complex is a 1.2 MDa chromatin modifying complex that can repress transcription by binding to gene promoters and deacetylating histones. The Sin3/HDAC complex can affect cell cycle progression through multiple mechanisms and is among the targets of anticancer drugs, called HDAC inhibitors. We describe the identification of a new subunit of the Sin3 complex named family with sequence similarity 60 member A (FAM60A). We show that FAM60A/Sin3 complexes normally suppress the epithelial-to-mesenchymal transition (EMT) and cell migration. This occurs through transcriptional repression of genes that encode components of the TGF-beta signaling pathway. This work reveals that FAM60A and the Sin3 complex are upstream repressors of TGF-beta signaling, EMT and cell migration and extends the known biological roles of the Sin3 complex. This experiment investigates the role of FAM60A in gene expression by comparing A549 lung cancer cells treated with or without siRNA against FAM60A.
Publication Title
Human family with sequence similarity 60 member A (FAM60A) protein: a new subunit of the Sin3 deacetylase complex.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
APCmin/+ mice develop spontaneous gastrointestinal polyposis due to a dominantly inhereited germline loss-of-function mutation in the tumor suppressor adenomatous polyposis coli (APC). Changes in intestinal immune activity have been documented to occur prior to the development of fulminate polyposis. Such changes are thought to contribute to disease development.
Publication Title
Oral interleukin-10 alleviates polyposis via neutralization of pathogenic T-regulatory cells.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
It is still unclear that how obesity increases the risk of breast cancer. To address this question, we used mRNA microarrays to characterize mouse breast tumor EO771 cells treated with mouse recombinant A-FABP protein and compared the data from their controls.
Publication Title
Circulating Adipose Fatty Acid Binding Protein Is a New Link Underlying Obesity-Associated Breast/Mammary Tumor Development.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 316 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Tissue material was collected from all breast cancer patients receiving surgery at Karolinska Hospital from 1994-1996. Material was frozen immediatley on dry ice or in liquid nitrogen and stored in -70C freezers. This series contains expression data for n=159 tumors from which RNA could be collected in sufficient amounts and quality for analysis.
Publication Title
Gene expression profiling spares early breast cancer patients from adjuvant therapy: derived and validated in two population-based cohorts.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 27 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This is a transcriptomics analysis contributing to a bigger project that tries to shed light on the role of type 2 diabetes mellitus (T2DM) as a risk factor for colon cancer (CC). Here we present a gene expression screening of paired tumor and normal colon mucosa samples in a cohort of 42 CC patients, 23 of them with T2DM. Using gene set enrichment, we identified an unexpected overlap of pathways over-represented in diabetics compared to non-diabetics, both in tumor and normal mucosa, including diabetes-related metabolic and signaling processes. An integration with other -omic studies suggests that in diabetics, the local micro-environment in normal colon mucosa may be a factor driving field cancerization which may promote carcinogenesis. Several of these pathways converged on the tumor initiation axis TEAD/YAP-TAZ. Cell culture studies confirmed that high glucose concentrations upregulate this pathway in non-tumor colon cells. In conclusion, diabetes is associated to deregulation of cancer-related processes in normal colon mucosa adjacent to tissue which has undergone a malignant transformation. These data support the existence of the field of cancerization paradigm in diabetes and set a new framework to study link between diabetes and cancer.
Publication Title
Molecular evidence of field cancerization initiated by diabetes in colon cancer patients.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This is a transcriptomics analysis contributing to a bigger project that tries to shed light on the role of type 2 diabetes mellitus (T2DM) as a risk factor for colon cancer (CC). Here we present a gene expression screening of 7 colon tumor xenograft samples, 2 with diabetic mice and 5 with normal blood glucose levels. For xenograft model details see: Prieto I, et al. (2017) Colon cancer modulation by a diabetic environment: A single institutional experience. PLoS One 12(3):e0172300
Publication Title
Molecular evidence of field cancerization initiated by diabetes in colon cancer patients.
Sample Metadata Fields
Specimen part
View Samples