Aberrant activation of FGFR3 via overexpression or mutation is a frequent feature of bladder cancer; however, its molecular and cellular consequences and functional relevance to carcinogenesis are not well understood. In this study with a bladder carcinoma cell line expressing inducible FGFR3 shRNAs, we sought to identiy transcriptional targets of FGFR3 and investigate their contribution to bladder cancer development.
FGFR3 stimulates stearoyl CoA desaturase 1 activity to promote bladder tumor growth.
Cell line
View SamplesHEK293T cells were transfected with the Rbp1-amr or slow (R729H-amr) -amanitin resistant subunit of RNA Pol II and selected with -amanitin 24 hours after transfection for additional 24 hours. Total RNA was extracted and global changes in gene expression were determined using microarray chips.
Disparity between microRNA levels and promoter strength is associated with initiation rate and Pol II pausing.
Cell line, Treatment
View SamplesApo2L/TRAIL stimulates cancer-cell death through the proapoptotic receptors DR4 and DR5, but the determinants of tumor susceptibility to this ligand are not fully defined. mRNA expression of the peptidyl O-glycosyl transferase GALNT14 correlated with Apo2L/TRAIL sensitivity in pancreatic carcinoma, non-small cell lung carcinoma and melanoma cell lines (P < 0.00009; n=83), and up to 30% of samples from various human malignancies displayed GALNT14 overexpression. RNA interference of GALNT14 reduced cellular Apo2L/TRAIL sensitivity, whereas overexpression increased responsiveness. Biochemical analysis of DR5 identified several ectodomain O-GalNAc-Gal-Sialic acid structures. Sequence comparison predicted conserved extracellular DR4 and DR5 O-glycosylation sites; progressive mutation of the DR5 sites attenuated apoptosis signaling. O-glycosylation promoted ligand-stimulated clustering of DR4 and DR5, which mediated recruitment and activation of the apoptosis-initiating protease caspase-8. These results uncover a novel link between death receptor O-glycosylation and apoptosis signaling, providing potential predictive biomarkers for Apo2L/TRAIL-based cancer therapy.
Death-receptor O-glycosylation controls tumor-cell sensitivity to the proapoptotic ligand Apo2L/TRAIL.
No sample metadata fields
View SamplesThe insulin-like growth factor (IGF) system consists of two ligands (IGF-I and IGF-II), which both signal through type I IGF receptor (IGF-IR) to stimulate proliferation and inhibit apoptosis, with activity contributing to malignant growth of many types of human cancers. We have developed a humanized, affinity-matured anti-human IGF-IR monoclonal antibody (h10H5), which binds with high affinity and specificity to the extracellular domain. h10H5 inhibits IGF-IR-mediated signaling by blocking IGF-I and IGF-IIbinding and by inducing cell surface receptor down-regulation via internalization and degradation. In vitro, h10H5 exhibits anti-proliferative effects on cancer cell lines. In vivo, h10H5 demonstrates single-agent anti-tumor efficacy in human SK-N-AS neuroblastoma and SW527 breast cancer xenograft models, and even greater efficacy in combination with the chemotherapeutic agent Docetaxel or an anti-VEGF antibody. Anti-tumor activity of h10H5 is associated with decreased AKT activation and glucose uptake, and a 316-gene transcription profile with significant changes involving DNA metabolic and cell cycle machineries. These data support the clinical testing of h10H5 as a biotherapeutic for IGF-IR-dependent human tumors.
Antixenograft tumor activity of a humanized anti-insulin-like growth factor-I receptor monoclonal antibody is associated with decreased AKT activation and glucose uptake.
No sample metadata fields
View SamplesYAP and TAZ play oncogenic roles in various organs, but the role of YAP/TAZ activation in gastric cancer in vivo has been understudied. We investigated whether and how YAP/TAZ initiates gastric tumorigenesis in vivo and its significance in human gastric cancer. We studied Lats1fl/fl;Lats2fl/fl;Lgr5-CreER mice, which have activated YAP/TAZ in pyloric stem cells. Gastric tissues were collected and analyzed by histopathology and immunostaining. To scrutinize the molecular mechanisms, we performed RNA sequencing in gastric tissue samples. Tissue microarray and public transcriptome data were analyzed to investigate the importance of YAP/TAZ in human gastric cancer. Overall design: Gastric pyloric tissue of Lats1fl/fl;Lats2fl/fl;Lgr5-CreER, or Lats1fl/fl;Lats2fl/fl mice that were 8 weeks after tamoxifen injection were collected in duplicates. RNAs were sequenced with Illumina NextSeq 500.
YAP/TAZ Initiates Gastric Tumorigenesis via Upregulation of MYC.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Competition between virus-derived and endogenous small RNAs regulates gene expression in Caenorhabditis elegans.
No sample metadata fields
View SamplesAnalysis of the transcriptional response to viral infection in C.elegans.
Competition between virus-derived and endogenous small RNAs regulates gene expression in Caenorhabditis elegans.
No sample metadata fields
View SamplesAttempt to identify small non-coding RNAs that change in levels as a result of viral infection of C.elegans Overall design: Small non-coding RNA (18-30nt) was extracted from animals either infected with Orsay virus or uninfected as indicated.
Competition between virus-derived and endogenous small RNAs regulates gene expression in Caenorhabditis elegans.
Cell line, Subject
View SamplesThe transition in developmental control from maternal to zygotic gene products marks a critical step in early embryogenesis. Here, we use GRO-seq analysis to map the genome-wide RNA polymerase distribution during the Drosophila maternal to zygotic transition. This analysis unambiguously identifies the zygotic transcriptome, and provides insight into its mechanisms of regulation. Overall design: Two replicates of GRO-seq at each time point.
Extensive polymerase pausing during Drosophila axis patterning enables high-level and pliable transcription.
Specimen part, Cell line, Subject, Time
View SamplesYeast cells were grown up in SD media containing all required amino acids. Each strain set was performed in triplicate. One set had no changes, the second set had 1mM methionine supplenting the media for the duration of growth and the third set was exposed to 0.5mM hydrogen peroxide for 15 minutes prior to harvesting
Gcn4 is required for the response to peroxide stress in the yeast Saccharomyces cerevisiae.
Compound
View Samples