The Hippo pathway effectors yes-associated protein (YAP) and WW domain containing transcription regulator 1 (TAZ/WWTR1) support tumor initiation and progression in various cancer entities including hepatocellular carcinoma (HCC). However, to which extent YAP and TAZ contribute to liver tumorigenesis via common and exclusive molecular mechanisms is poorly understood. RNAinterference (RNAi) experiments illustrate that YAP and TAZ individually support HCC cell viability and migration, while for invasion additive effects were observed. Comprehensive expression profiling revealed partly overlapping YAP/TAZ target genes as well as exclusively regulated genes.
TAZ target gene ITGAV regulates invasion and feeds back positively on YAP and TAZ in liver cancer cells.
Specimen part, Cell line
View SamplesTotal RNA was isolated from HuH-7 cells after transfection of IGF-II specific siRNAs. Gene expression profiling was performed using the Affymetrix Human Genome U133A 2.0 Arrays. The raw data were analysed using mixed model ANOVA.
Autocrine insulin-like growth factor-II stimulation of tumor cell migration is a progression step in human hepatocarcinogenesis.
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View SamplesAdam17, a shedding protease, is strongly upregtulated during inflammation and cancer. Here we investigate the genome wide effects of Adam17 knock out on the transcriptome.
Critical role of the disintegrin metalloprotease ADAM17 for intestinal inflammation and regeneration in mice.
Specimen part
View SamplesCell polarity is crucial for the maintenance of epithelial cell function and its loss may have an im-portant role in the development and progression of cancer. We here show that overexpression and cytoplasmic enrichment of the baso-lateral polarity complex protein Scribble (Scrib) correlates with poor prognosis of hepatocellular cancer (HCC) patients. Expression of the cytoplasmic ScribP305L in hepatocellular cells induces epithelial to mesenchymal transition (EMT) and supports HCC cell invasion in comparison to cells expressing membrane-localized ScribWT. ScribP305L induces AKT signalling through destabilization of the phosphatases phosphatase and tensin homolog (PTEN) and PH domain and leucine rich repeat protein phosphatase 1 (PHLPP1). Moreover, cytoplasmic ScribP305L stimulates the expression of secreted protein acidic and cysteine rich (SPARC) de-pending on the AP1 constituents ATF2 and JunB, which drives HCC cell invasiveness. In vivo, combined hydrodynamic delivery of ScribP305L but not ScribWT and c-MYC initiates tumour for-mation in hepatocytes and cytoplasmic Scrib correlates with AKT phosphorylation, and AP1 ex-pression in human HCC tissues. Together, overexpression and mislocalization of Scrib represents an early event involved in the initiation and progression of liver cancer.
Cytoplasmic localization of the cell polarity factor scribble supports liver tumor formation and tumor cell invasiveness.
Cell line
View SamplessiRNA-mediated inhibition compared to untreated cells and cells transfected with nonsense siRNA
Overexpression of far upstream element (FUSE) binding protein (FBP)-interacting repressor (FIR) supports growth of hepatocellular carcinoma.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrative DNA methylation and gene expression analysis in high-grade soft tissue sarcomas.
Sex, Age
View SamplesWe used the Infinium HumanHT-12 platform to profile gene expression in 79 primary, untreated high-grade soft tissue sarcomas, representing eight relevant subtypes, two non-neoplastic fat samples and 13 representative sarcoma cell lines.
Integrative DNA methylation and gene expression analysis in high-grade soft tissue sarcomas.
Sex
View SamplesMost lung adenocarcinoma deaths are related to metastases, indicating the necessity of detecting and inhibiting tumor cell dissemination. We have identified that overexpression of miRNAs located on 14q32 was associated with metastasis in lung adenocarcinoma patients. For functional analysis, we utilized CRISPR activation technology to increase levels of miRNAs clustered on 14q32 in a coordinated manner, and the results showed that 14q32 miRNA overexpression promoted tumor cell migratory and invasive properties. Whole transcriptome microarray analysis of the miRNA-overexpressing cells was performed to define the underlying molecular mechanisms.
Epigenetically Regulated Chromosome 14q32 miRNA Cluster Induces Metastasis and Predicts Poor Prognosis in Lung Adenocarcinoma Patients.
Specimen part, Cell line
View SamplessiRNA-mediated inhibition compared to untreated cells and cells transfected with nonsense siRNA.
Yes-associated protein up-regulates Jagged-1 and activates the Notch pathway in human hepatocellular carcinoma.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Tissue-specific NETs alter genome organization and regulation even in a heterologous system.
Cell line, Treatment
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