The tumor microenvironment plays a critical role in cancer progression, but the precise mechanisms by which stromal cells influence the tumor epithelium are poorly understood. The signaling adapter p62 has been implicated as a positive regulator of epithelial tumorigenesis; however, its role in the stroma is unknown. We show here that p62 levels are reduced in the stroma of several tumors. Also, orthotopic and organotypic studies demonstrate that the loss of p62 in the tumor microenvironment or stromal fibroblasts resulted in increased tumorigenesis of epithelial prostate cancer cells. The mechanism involves the regulation of cellular redox through an mTORC1/c-Myc pathway of stromal glucose and amino acid metabolism. Inhibition of the pathway by p62 deficiency results in increased stromal IL-6 production, which is required for tumor promotion in the epithelial compartment. Thus, p62 is an anti-inflammatory tumor suppressor that acts through modulation of metabolism in the tumor stroma.
Metabolic reprogramming of stromal fibroblasts through p62-mTORC1 signaling promotes inflammation and tumorigenesis.
Specimen part
View SamplesHypoxia is a low oxygen condition that occurs in the developing tumor mass and that is associated with poor prognosis and resistance to chemo- and radio-therapy. The definition of the hypoxia gene signature is fundamental for the understanding of tumor biology, as in the case of neuroblastoma, the most common pediatric solid tumor. The issue of identifying a significant group of variables in microarray gene expression experiments is particularly difficult due to the typical high dimensional nature of the data and great effort has been spent in the development of feature selection techniques.
The l1-l2 regularization framework unmasks the hypoxia signature hidden in the transcriptome of a set of heterogeneous neuroblastoma cell lines.
Cell line
View SamplesHypoxia is a low oxygen condition that occurs in the developing tumor mass and that is associated with poor prognosis and resistance to chemo- and radio-therapy. The definition of the hypoxia gene signature is fundamental for the understanding of tumor biology, as in the case of neuroblastoma, the most common pediatric solid tumor. The issue of identifying a significant group of variables in microarray gene expression experiments is particularly difficult due to the typical high dimensional nature of the data and great effort has been spent in the development of feature selection techniques.
A biology-driven approach identifies the hypoxia gene signature as a predictor of the outcome of neuroblastoma patients.
Cell line
View SamplesThe bone marrow microenvironment in Large Granular Lymphocyte Leukemia (LGLL) patients has been unexplored for its role in the development of cytopenias, which lead to complications resulting in the most prominent causes of morbidity and mortality.
Fibrosis and subsequent cytopenias are associated with basic fibroblast growth factor-deficient pluripotent mesenchymal stromal cells in large granular lymphocyte leukemia.
Specimen part, Disease, Disease stage
View SamplesA split-split-plot design with 144 experimental units (3 replications x 4 genotypes x 6 time points x 2 treatment types) was used to profile barley plants containing variants of Mla1 and Mla6 powdery mildew resistance genes in response to inoculation with the Blumeria graminis f. sp. hordei (Bgh) isolates 5874 (AvrMla1, AvrMla6). Barley leaves were harvested from inoculated and non-inoculated plants at 6 time points (0,8,16,20,24 and 32 hrs) after Bgh inoculation. ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Rico Caldo. The equivalent experiment is BB10 at PLEXdb.]
Blufensin1 negatively impacts basal defense in response to barley powdery mildew.
Specimen part, Time
View SamplesBarley stripe mosaic virus-induced gene silencing (BSMV-VIGS) was used to identify significant new genes in the regulation of host innate immunity. This experiment was designed to uncover significant changes in Bln1 (Contig12219_at)-silenced plants relative to empty vector and buffer treated controls. Five independent biological replications of a split-plot experimental design were conducted with replications as blocks, treatment with Blumeria graminis f. sp. hordei (Bgh) as the whole-plot factor, and all combinations of genotype (Mla13 and Mla9) and VIGS treatment [Buffer control (mock), BSMV:00 (empty vector), and BSMV:Bln1248] as the split-plot factor for a total of 60 GeneChip hybridizations. Ten seedlings were used as a split-plot experimental unit for each combination of replication, Bgh treatment, genotype, and VIGS treatment. Plants were grown in a controlled 20C glasshouse prior to VIGS treatment. Twelve days after VIGS treatment, half of the plants in each replication were challenged with the compatible Bgh isolate 5874. Top halves of 5 of the 10 seedling third leaves (about 10 cm) from each split-plot experimental unit were harvested into liquid N2 at 32 hours after inoculation (HAI) - the timepoint with the highest differential Bln1 transcript accumulation (Meng et al. 2009), and after initial establishment of the perihaustorial interface (Caldo et al. 2004). The remaining 5 leaves were used to record infection phenotype 7 days later. RNA was isolated for GeneChip hybridization from the 32-HAI samples. ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Yan Meng. The equivalent experiment is BB101 at PLEXdb.]
Blufensin1 negatively impacts basal defense in response to barley powdery mildew.
Age, Specimen part
View SamplesA parallel expression profiling of wild-type and loss-of-function mutants of Mla6 and Mla1 powdery mildew resistance alleles was conducted using Barley1 GeneChip. Barley plants were inoculated with powdery mildew isolate 5874 and first leaves were harvested at 6 time points after pathogen inoculation. This experiment was conducted in split-split-plot experimental design with 3 replications.
Blufensin1 negatively impacts basal defense in response to barley powdery mildew.
Age, Specimen part, Time
View SamplesDespite advances in surgery and radiotherapy of uveal melanoma (UM), many patients develop distant metastases that poorly respond to therapy. Improved therapies for the metastatic disease are therefore urgently needed. Expression of the epidermal growth factor receptor (EGFR), a target of kinase inhibitors and humanized antibodies in use for several cancers, had been reported. 48 human UMs were analyzed by expression profiling. Evidence for signaling in tumors was obtained through the application of a UM-specific EGF signature. The EGFR specific kinase inhibitor, Gefitinib, and the humanized monoclonal antibody, Cetuximab, were tested for their effect on EGFR signaling. Natural killer cell mediated antibody-dependent cellular cytotoxicity (ADCC) and TNF-alpha release was analyzed for Cetuximab. EGFR appears suited as a novel molecular drug target for therapy of uveal melanoma.
Evidence of epidermal growth factor receptor expression in uveal melanoma: inhibition of epidermal growth factor-mediated signalling by Gefitinib and Cetuximab triggered antibody-dependent cellular cytotoxicity.
Sex, Specimen part, Disease, Disease stage
View SamplesA-to-I RNA editing levels differ across tissues and cell types, but regulators of the editing process are largely unknown. We used RNA-seq on whole fly brains with different RNA binding proteins knocked down to test for A-to-I RNA editing level differences between controls and knockdowns. Overall design: To screen for editing regulators in the Drosophila brain, we crossed a pan-neuronal Gal4 driver, C155-Gal4, to different UAS-shRNA lines targeting individual RNA binding proteins, extracted RNA and made RNA-seq libraries. We sequenced four total replicates of shGFP controls and two replicates of all RNA binding protein knockdowns.
Zinc Finger RNA-Binding Protein Zn72D Regulates ADAR-Mediated RNA Editing in Neurons.
Sex, Specimen part, Subject
View SamplesCategorisation of LGGs related to their lesion site (infratentorial vs. supratentorial)
Molecular fingerprinting reflects different histotypes and brain region in low grade gliomas.
No sample metadata fields
View Samples