We compared gene and protein expression profiles in cells challenged with ER stress-inducing drugs or expressing model polypeptides. Drugs titration to limit up-regulation of the endogenous ER stress reporters BiP/HSPA5 and HERP/HERPUD1 to levels comparable to luminal accumulation of unfolded proteins substantially reduced the amplitude of transcriptional and translational responses.
No associated publication
Cell line, Treatment
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 Samplesassess the efficacy of dual PI3K/mTOR inhibitor with anti-lymphoma activity as single agent and in combination
PQR309 Is a Novel Dual PI3K/mTOR Inhibitor with Preclinical Antitumor Activity in Lymphomas as a Single Agent and in Combination Therapy.
Specimen part, Cell line, Treatment
View Samplesassess the gene expression profiling of 61 cell lines
PQR309 Is a Novel Dual PI3K/mTOR Inhibitor with Preclinical Antitumor Activity in Lymphomas as a Single Agent and in Combination Therapy.
Specimen part, Cell line
View SamplesGenetic knockdown or chemical inhibitors of BRD4 elicited different biological responses in bulk tumor cells in 2D cultures and CSC-enriched tumor-sphere cultures. Gene profiling revealed that BRD4 inhibition affected different sets of genes in two cell contexts. BRD4 drives a CSC-specific transcriptional programs that can be disrupted by chemical inhibitors causing exhaustion and elimination of prostate CSCs.
No associated publication
Specimen part, Cell line, Treatment
View SamplesAssess the efficacy of trabectedin in two DLBCL cell lines
Trabectedin is a novel chemotherapy agent for diffuse large B cell lymphoma.
Treatment, Time
View SamplesBy utilizing mast cells lacking Dnmt3a, we found that this enzyme is involved in restraining mast cell responses to stimuli, both in vitro and in vivo.
<i>Dnmt3a</i> restrains mast cell inflammatory responses.
Sex, Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
No associated publication
Specimen part, Cell line
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 Sampleswe evaluated the mechanism behind NOTCH activation in prostate cancer
Inhibition of Notch pathway arrests PTEN-deficient advanced prostate cancer by triggering p27-driven cellular senescence.
Specimen part
View Samples