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SRP121474
Homo sapiens
9 Downloadable Samples
Illumina HiSeq 2500
Description
Cancer cells alter their metabolism to support their malignant properties. By transcriptomic analysis we identified the glucose-transforming polyol pathway (PP) gene aldo-keto-reductase-1-member-B1 (AKR1B1) as strongly correlated with epithelial-to-mesenchymal transition (EMT). This association was confirmed staining samples from lung cancer patients and from an EMT-driven colon cancer mouse model with p53 deletion. In vitro, mesenchymal-like cancer cells showed increased AKR1B1 levels and AKR1B1 knockdown was sufficient to revert EMT. An equivalent level of EMT suppression was measured by targeting the downstream enzyme sorbitol-dehydrogenase (SORD), further pointing at the involvement of the PP. Comparative RNA sequencing profiling confirmed a profound alteration of EMT in PP-deficient cells, revealing a strong repression of TGF-Beta signature genes. Mechanistically, excess glucose was found to promote EMT through autocrine TGF-Beta stimulation, while PP-deficient cells were refractory to glucose-induced EMT. PP represents a molecular link between glucose metabolism and cancer differentiation and aggressiveness, and a novel potential therapeutic target. Overall design: 3x3 biological replicated samples; 2 groups of samples with shRNA-mediated specific gene inhibition and scrambled control cells
Publication Title
Polyol Pathway Links Glucose Metabolism to the Aggressiveness of Cancer Cells.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Sus scrofa
- 6 Downloadable Samples
Affymetrix Porcine Genome Array (porcine)
Description
The maternal tract plays a critical role in the success of early embryonic development providing an optimal environment for establishment and maintenance of pregnancy. Preparation of this environment requires an intimate dialogue between the embryo and her mother. To advance our understanding of the process by which a foreign blastocyst is accepted by the maternal endometrium and better address the clinical challenges of infertility and pregnancy failure, it is imperative to decipher this complex molecular dialogue. The objective of the present work is to define the local response(s) of the maternal tract towards the embryo during the earliest stages of pregnancy.
Publication Title
Early developing pig embryos mediate their own environment in the maternal tract.
Sample Metadata Fields
Specimen part, Disease
View Samples- Sus scrofa
- 8 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
The objective of the present study is to investigate if females have the ability to recognise X or Y chromosome bearing spermatozoa and present a different response to different spermatozoa.
Publication Title
The battle of the sexes starts in the oviduct: modulation of oviductal transcriptome by X and Y-bearing spermatozoa.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Briefly, the well characterized female hES cell line H9 was allowed to differentiate into a clonally purified mortal splanchnopleuric mesodermal somatic cell line EN13. The EN13 line was subsequently virally reprogrammed back to an induced pluripotent state (we term re-H9) using OCT4, SOX2, KLF4 retroviral vectors creating isogenic lines of hESC, hiPSC and mortal cells. Our results reveal several important differences between embryo-derived H9 and the induced re-H9 stem cells. We find a dysregulation of genes involved in imprinting and altered expression of X-chromosome localized genes in re-H9 cells.
Publication Title
Suppression of the imprinted gene NNAT and X-chromosome gene activation in isogenic human iPS cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Rescuing the function of mutant p53 protein is an attractive cancer therapeutic strategy. Using the NCI anticancer drug screen data, we identified two compounds from the thiosemicarbazone family that manifest increased growth inhibitory activity in mutant p53 cells, particularly for the p53R175 mutant. Mechanistic studies reveal that NSC319726 restores WT structure and function to the p53R175 mutant. This compound kills p53R172H knock-in mice with extensive apoptosis and inhibits xenograft tumor growth in a 175-allele specific mutant p53 dependent manner. This activity depends upon the zinc ion chelating properties of the compound as well as redox changes. These data identify NSC319726 as a p53R175 mutant reactivator and as a lead compound for p53 targeted drug development.
Publication Title
Allele-specific p53 mutant reactivation.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 16 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Analysis of different iPSC clones in comparison to parental fibroblasts and Pluripotent ESC and iPSC lines
Publication Title
CD44 is a negative cell surface marker for pluripotent stem cell identification during human fibroblast reprogramming.
Sample Metadata Fields
Cell line
View Samples- Schizosaccharomyces pombe
- 12 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
In addition to its well-know function in chromosome segregation, increasing evidence implicates cohesin in the control of gene expression. It has been previously reported that inactivation of the cohesin loader Mis4 in G1-arrested cells leads to the dissociation of cohesin from chromatin. We exploited this experimental situation to ask whether this loss of cohesin would affect gene expression on a genome-wide scale.
Publication Title
Role for cohesin in the formation of a heterochromatic domain at fission yeast subtelomeres.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Chemotherapy resistance presents a major hurdle for cancer treatment. We proposed to identify the molecular changes through which breast cancer cells evolve resistance to conventional treatment, here cisplatin, so targeted therapy can be developed. Candidate approach RNAi screening was combined with cisplatin treatment in order to identify molecular pathways conferring survival advantages. The screening identified ATP7A, a copper transport ATPase responsible for the intercellular movement and sequestering of cisplatin, as a therapeutic target. Copper chelation with tetrathiomolybdate (TM) targets ATP7A. TM in combination with cisplatin sensitized drug-resistant breast cancer cells. Allograft and xenograft models in aythymic mice treated with TM/cisplatin combination therapy inhibited tumor growth and increased survival compared with monotreated mice. Examination of the molecular effects of TM on cisplatin efficacy in drug-resistant tumors revealed reduced levels of APT7A, reduced cisplatin sequestering by ATP7A and increased nuclear availability of cisplatin. Further, we showed that TM treatment combined with cisplatin reduced the half-life of ATP7A in human breast cancer cell lines. This finding offered the potential to combat drug platinum-resistant tumors and sensitize patients to conventional breast cancer treatments by identifying and targeting resistant tumors unique molecular adaptations.
Publication Title
Ammonium tetrathiomolybdate treatment targets the copper transporter ATP7A and enhances sensitivity of breast cancer to cisplatin.
Sample Metadata Fields
Cell line, Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mitochondrial oxidative function is tightly controlled to maintain energy homeostasis in response to nutrient and hormonal signals. An important cellular component in the energy sensing response is the target of rapamycin (TOR) kinase pathway; however whether and how mTOR controls mitochondrial oxidative activity is unknown. Here, we show that mTOR kinase activity stimulates mitochondrial gene expression and oxidative function. In skeletal muscle cells and TSC2-/- MEFs, the mTOR inhibitor rapamycin largely decreased gene expression of mitochondrial transcriptional regulators such as PGC-1alpha and the transcription factors ERRalpha and NRFs. As a consequence, mitochondrial gene expression and oxygen consumption were reduced upon mTOR inhibition. Using computational genomics, we identified the transcription factor YY1 as a common target of mTOR and PGC-1alpha that controls mitochondrial gene expression. Inhibition of mTOR resulted in a failure of YY1 to interact and be coactivated by PGC-1alpha. Notably, knock-down of YY1 in skeletal muscle cells caused a significant decrease in mRNAs of mitochondrial regulators and mitochondrial genes that resulted in a decrease in respiration. Moreover, YY1 was required for rapamycin-dependent repression of mitochondrial genes. Thus, we have identified a novel mechanism in which a nutrient sensor (mTOR) balances energy metabolism via transcriptional control of mitochondrial oxidative function. These results have important implications for our understanding of how these pathways might be altered in metabolic diseases and cancer.
Publication Title
mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
miR-30e targets IGF2-regulated osteogenesis in bone marrow-derived mesenchymal stem cells, aortic smooth muscle cells, and ApoE-/- mice.
Sample Metadata Fields
Specimen part, Treatment
View Samples