Our findings demonstrate that CDCP1 is a novel modulator of HER2 signalling, and a biomarker for the stratification of breast cancer patients with poor prognosis
Interaction of CDCP1 with HER2 enhances HER2-driven tumorigenesis and promotes trastuzumab resistance in breast cancer.
Cell line
View SamplesKeratinocytes isolated from one healthy donor were stimulated in triplicate for 24h with IL-36a, IL-36ß or IL-36? Overall design: Gene expression profile of IL-36 stimulated keratinocytes
An analysis of IL-36 signature genes and individuals with <i>IL1RL2</i> knockout mutations validates IL-36 as a psoriasis therapeutic target.
Specimen part, Subject
View SamplesAmong B-cell lymphomas mantle cell lymphoma (MCL) has the worst prognosis. By using a combination of genomic and expression profiling (Affymetrix GeneChip Mapping 10k Xba131 and U133 set), we analysed 26 MCL samples to identify genes relevant to MCL pathogenesis and that could represent new therapeutic targets. Recurrent genomic deletions and gains were detected. Genes were identified as overexpressed in regions of DNA gain on 3q, 6p, 8q, 9q, 16p and 18q, including the cancer genes BCL2 and MYC. Among the transcripts with high correlation between DNA and RNA, we identified SYK, a tyrosine kinase involved in B-cell receptor signalling. SYK was amplified at DNA level, as validated by fluorescence in situ hybridisation (FISH) analysis, and overexpressed at both RNA and protein levels in the JeKo-1 cell line. Low-level amplification, with protein overexpression of Syk was demonstrated by FISH in a small subset of clinical samples. After treatment with low doses of the Syk inhibitor piceatannol, cell proliferation arrest and apoptosis were induced in the cell line overexpressing Syk, while cells expressing low levels of Syk were much less sensitive. A combination of genomic and expression profiling suggested Syk inhibition as a new therapeutic strategy to be explored in lymphomas.
Genomic and expression profiling identifies the B-cell associated tyrosine kinase Syk as a possible therapeutic target in mantle cell lymphoma.
No sample metadata fields
View SamplesMetabolism in cancer serves to provide energy and key biomolecules that sustain cell growth, a process that is frequently accompanied by decreased mitochondrial use of glucose. Importantly, metabolic intermediates including mitochondrial metabolites are central substrates for post-translational modifications at the core of cellular signalling and epigenetics. However, the molecular means that coordinate the use of mitochondrial metabolites for anabolism and nuclear protein modification are poorly understood. Here, we unexpectedly found that genetic and pharmacological inactivation of Pyruvate Dehydrogenase A1 (PDHA1), a subunit of pyruvate dehydrogenase complex (PDC) that regulates mitochondrial metabolism16 inhibits prostate cancer development in different mouse and human xenograft tumour models. Intriguingly, we found that lipid biosynthesis was strongly affected in prostate tumours upon PDC inactivation. Mechanistically, we found that nuclear PDC controls the expression of Sterol regulatory element-binding transcription factor (SREBF) target genes by mediating histone acetylation whereas mitochondrial PDC provides cytosolic citrate for lipid synthesis in a coordinated effort to sustain anabolism. In line with the oncogenic function of PDC in prostate cancer, we find that PDHA1 and the PDC activator, Pyruvate dehydrogenase phospatase 1 (PDP1), are frequently amplified and overexpressed at both gene and protein level in these tumours. Taken together, our findings demonstrate that both mitochondrial and nuclear PDC sustains prostate tumourigenesis by controlling lipid biosynthesis thereby pointing at this complex as a novel target for cancer therapy.
Compartmentalized activities of the pyruvate dehydrogenase complex sustain lipogenesis in prostate cancer.
No sample metadata fields
View SamplesBackground: Changes in gene regulation are thought to be crucial for the adaptation of organisms to their environment. Transcriptome analyses can be used to identify candidate genes for ecological adaptation, but can be complicated by variation in gene expression between tissues, sexes, or individuals. Here we use high-throughput RNA sequencing of a single Drosophila melanogaster tissue to detect brain-specific differences in gene expression between the sexes and between two populations, one from the ancestral species range in sub-Saharan Africa and one from the recently colonized species range in Europe. Results: Relatively few genes (<100) displayed sexually dimorphic expression in the brain, but there was an enrichment of sex-biased genes, especially male-biased genes, on the X chromosome. Over 340 genes differed in brain expression between flies from the African and European populations, with the between-population divergence being highly correlated between males and females. The differentially expressed genes include those involved in stress response, olfaction, and detoxification. Expression differences were associated with transposable element insertions at two genes implicated in insecticide resistance (Cyp6g1 and CHKov1). Conclusions: Analysis of the brain transcriptome revealed many genes differing in expression between populations that were not detected in previous studies using whole flies. There was little evidence for sex-specific regulatory adaptation in the brain, as most expression differences between populations were observed in both males and females. The enrichment of genes with sexually dimorphic expression on the X chromosome is consistent with dosage compensation mechanisms affecting sex-biased expression in somatic tissues. Overall design: mRNA profiles of Drosophila melanogaster brains from adult males and females from a European and an African population (2 biological replicates each)
Population and sex differences in Drosophila melanogaster brain gene expression.
Sex, Subject
View SamplesPost-translational modifications of proteins by Small Ubiquitin-like Modifiers (SUMOs) regulate protein degradation and localization, protein-protein interaction, and transcriptional activity. SUMO E3 ligase functions are executed by SIZ1/SIZ2 in yeast and PIAS family members in human. The Arabidopsis genome contains only one gene, SIZ1, that is orthologous to yeast SIZ1/SIZ2. Here, we show that the Arabidopsis SIZ1 interacts with SUM1 and SCE1a, the SUMO E2 conjugating enzyme. Compared to WT, the null mutant siz-1-3 is smaller in statue because of reduced expression of gene involved in brassinosteroid biosynthesis and signalling. Drought stress induces the accumulation of SUMO-protein conjugates, which is in part dependent on SIZ1 but not on ABA. Mutant plants of siz1-3 have significant lower tolerance to drought stress. Genome wide expression analysis identified about 2,000 Arabidopsis genes that are responsive to drought, and SIZ1 mediates the induction of 600 of these genes by a pathway independent of DREB2A and ABA. SIZ1-dependent, drought-responsive genes include those encoding enzymes of the anthocyanin synthesis pathway and jasmonate response. From these results, we conclude that SIZ1 regulates Arabidopsis development and plays a role in drought stress response probably through the control of gene expression.
The Arabidopsis E3 SUMO ligase SIZ1 regulates plant growth and drought responses.
Age
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Amygdalar MicroRNA-15a Is Essential for Coping with Chronic Stress.
Specimen part
View SamplesTo identify genes important in fetal preparation for birth.
Developmental control of the Nlrp6 inflammasome and a substrate, IL-18, in mammalian intestine.
Specimen part
View SamplesWe report the role of LSM1-7 complex in the Arabidopsis tolerance to abiotic stresses. LSM1-7 controls gene expression reprogramming at the post-transcriptional level by promoting the decapping of mRNA. This function is selectively achieve over selected stress-induced transcripts depending on stress nature. Overall design: Comparison of transcriptomes from Col-0 and lsm1a lsm1b plants exposed to low temperatures, drought or high salt conditions
The LSM1-7 Complex Differentially Regulates Arabidopsis Tolerance to Abiotic Stress Conditions by Promoting Selective mRNA Decapping.
Specimen part, Subject
View SamplesWe report the role of SmE1 protein in the control of Arabidopsis development and tolerance to abiotic stresses. SmE1 controls gene expression reprogramming at the post-transcriptional level by promoting the splicing of pre-mRNA. This function is selectively achieve over selected transcripts depending on the stimulus nature. Overall design: Transcriptomic profiling through RNAseq of Col-0 and sme1-1 plants under control conditions or exposed to low temperatures (4ºC, 24h)
Arabidopsis SME1 Regulates Plant Development and Response to Abiotic Stress by Determining Spliceosome Activity Specificity.
Specimen part, Subject
View Samples