Epidemiological studies have revealed concurrence of specific cancers with other disease states such as metabolic syndrome, inflammatory disease and autoimmune disease. Patients with these chronic conditions have a higher incidence of various cancers, more aggressive tumors, and a higher mortality rate. It has been proposed that obesity, inflammation and chronic disease should be correlated with cancer at the molecular level, but common gene signatures or networks have yet to be described. Here, we identify genes regulated during the process of cellular transformation in both a breast epithelial cell line and a set of isogenic fibroblastic cell lines.
A transcriptional signature and common gene networks link cancer with lipid metabolism and diverse human diseases.
Cell line, Time
View SamplesNLRC5 is a member of the NLR family of proteins. The observation that NLRC5 is found in the nucleus prompted us to perform a gene array to identify putative target genes of NLRC5. We generated Jurkat T cell lines that stably express either the wild-type or mutant forms of NLRC5 harboring mutations in the nucleotide binding domain (NBD): Walker A (deficient in nucleotide binding), Walker B (deficient in nucleotide hydrolysis), and the combined Walker AB, carrying both mutations.
NLR family member NLRC5 is a transcriptional regulator of MHC class I genes.
Cell line
View SamplesCells transiently adapt to hypoxia by globally decreasing protein translation. However, specific proteins needed to respond to hypoxia evade this translational repression. The mechanisms of this phenomenon remain unclear. We screened for and identified small molecules that selectively decrease HIF-2a translation in an mTOR independent manner, by enhancing the binding of Iron Regulatory Protein 1 (IRP1) to a recently reported Iron-Responsive Element (IRE) within the 5-untranslated region (UTR) of the HIF-2a message. Knocking down the expression of IRP1 by shRNA abolished the effect of the compounds. Hypoxia de-represses HIF-2a translation by disrupting the IRP1- HIF-2a IRE interaction. Thus, this chemical genetic analysis describes a molecular mechanism by which translation of the HIF-2a message is maintained during conditions of cellular hypoxia through inhibition of IRP-1 dependent repression. It also provides the chemical tools for studying this phenomenon.
Small-molecule inhibitors of HIF-2a translation link its 5'UTR iron-responsive element to oxygen sensing.
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View SamplesDifferential gene expression profiling in PPP2R2A depleted RT-112 cells was performed using Human Genome U133 Plus 2.0 Array
MKAD-21 Suppresses the Oncogenic Activity of the miR-21/PPP2R2A/ERK Molecular Network in Bladder Cancer.
Specimen part, Cell line
View SamplesDifferential gene expression profiling in KMT2D-depleted MIA PaCa-2 cells was performed using Human Genome U133 Plus 2.0 Array
Lysine methyltransferase 2D regulates pancreatic carcinogenesis through metabolic reprogramming.
Treatment
View SamplesGene expression was analyzed and compared of normal mouse hepatocyte, premalignant hepatocytes and fully malignant HCC cells. The results provide valuable information about the gene expression alterations during the chronic process of liver cancer development.
Identification of liver cancer progenitors whose malignant progression depends on autocrine IL-6 signaling.
Specimen part
View SamplesSIRT6 is a member of a highly conserved family of NAD+-dependent deacetylases with various roles in metabolism, stress resistance, and life span. SIRT6- deficient mice develop normally but succumb to a lethal hypoglycemia early in life; however, the mechanism underlying this hypoglycemia remained unclear. Here, we demonstrate that SIRT6 functions as a histone H3K9 deacetylase to control the expres- sion of multiple glycolytic genes. Specifically, SIRT6 appears to function as a corepressor of the transcrip- tion factor Hif1a, a critical regulator of nutrient stress responses. Consistent with this notion, SIRT6-defi- cient cells exhibit increased Hif1a activity and show increased glucose uptake with upregulation of glycolysis and diminished mitochondrial respiration. Our studies uncover a role for the chromatin factor SIRT6 as a master regulator of glucose homeostasis and may provide the basis for novel therapeutic approaches against metabolic diseases, such as diabetes and obesity.
The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
XBP1 promotes triple-negative breast cancer by controlling the HIF1α pathway.
Specimen part, Cell line
View SamplesDuring cancer progression, carcinoma cells encounter a variety of cytotoxic stresses such as hypoxia, nutrient deprivation, and low pH as a result of inadequate vascularization. To maintain survival and growth in the face of these physiologic stressors, a set of adaptive response pathways are induced. One adaptive pathway well studied in other contexts is the unfolded protein response (UPR), of which XBP1 is an important component.
XBP1 promotes triple-negative breast cancer by controlling the HIF1α pathway.
Cell line
View SamplesWe compared different mouse cancer cell lines to identify their unique cell signatures.
Myeloid-derived interleukin-1β drives oncogenic KRAS-NF-κΒ addiction in malignant pleural effusion.
Cell line, Treatment
View Samples