Transcriptional responses of human colon and liver cancer cells to TCF inhibition.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE46465 | GEO | 2013/08/01
SECONDARY ACCESSION(S): PRJNA200691
REPOSITORIES: GEO
Similar Datasets
Project description:Dysregulation of Wnt/TCF signaling is closely associated with cancers arising from the gastrointestinal tract, inlcluding colon cancer and liver cancer. The goal of this study is to understand the transcriptional programs underlying Wnt/TCF activation in gastrointestinal cancers. We examined the transcriptional responses to TCF inhibition in cultured human colon cancer cells and liver cancer cells that are characteristic of Wnt pathway activation. Human liver cancer cell line HepG2 and colon cancer cell line LS174T with or without expression of a dominant negative form of TCF4
2013-08-01 | E-GEOD-46465 | biostudies-arrayexpress
Project description:The WNT-TCF signaling pathway participates in adult tissue homeostasis and repair, and is hyperactive in a number of human diseases including cancers of the colon. Whereas to date there are no antagonists approved for patient use, a potential problem for their sustained use is the blockade of WNT signaling in healthy tissues, thus provoking potentially serious co-lateral damage. Here we have screened a library of plant and microorganism small molecules for novel WNT signaling antagonists and describe withanolide F as a potent WNT-TCF response blocker. This steroidal lactone inhibits TCF-dependent colon cancer xenograft growth and mimics the effects of genetic blockade of TCF and of ivermectin, a previously reported WNT-TCF blocker. However, withanolide F is unique in that it imposes a long-lasting repression of tumor growth, WNT-TCF targets and cancer stem cell clonogenicity long after drug treatment
2017-02-22 | GSE87874 | GEO
Project description:The effect of ER-stress and subsequent activation of the unfolded protein response was investigated in colon cancer stem cells and more differentiated colon cancer cells Human colon cancer derived spheroid cultures with a TCF/LEF driven GFP reporter for Wnt signaling activity were treated for 24 hours with SubAB or protease-dead SubABco (1µg/ml) Treated spheroid cultures were sorted into colon-cancer stem cell fraction (highest 10% Wnt-GFP) and differentiated colon cancer fraction (10% Lowest(Wnt Low) for micro array
2015-02-12 | E-GEOD-65879 | biostudies-arrayexpress
Project description:Background & Aims. Sporadic colorectal cancers arise from mutations in APC, producing oncogenic β-catenin/TCF-dependent transcriptional reprogramming. The tumor suppressor axis regulated by the intestinal epithelial receptor, GUCY2C, is among the earliest pathways silenced in tumorigenesis. Retention of the receptor, but loss of its paracrine ligands, guanylin and uroguanylin, is an evolutionarily conserved feature of colorectal tumors, arising in the earliest dysplastic lesions. Here, we examined a mechanism of GUCY2C ligand transcriptional silencing by β-catenin/TCF signaling. Methods. We performed RNA-seq analysis of four unique conditional human colon cancer cell models of β-catenin/TCF signaling to map the core Wnt-transcriptional program. We then performed a comparative analysis of orthogonal approaches, including luciferase reporters, ChIP-seq, CRISPR Cas9 knockout, and CRISPR epigenome editing, which were cross-validated with human tissue ChIP-seq datasets, to identify functional gene enhancers mediating GUCY2C ligand loss. Results. RNA-seq analyses reveal the GUCY2C hormones as two of the most sensitive targets of β-catenin/TCF signaling, reflecting transcriptional repression. The GUCY2C hormones share an insulated genomic locus containing a novel locus control region upstream of the guanylin promoter that mediates the coordinated silencing of both genes. Targeting this region with CRISPR epigenome editing reconstituted GUCY2C ligand expression, overcoming gene inactivation by mutant β-catenin/TCF signaling. Conclusions. These studies reveal novel DNA elements regulating co-repression of GUCY2C ligand transcription by β-catenin/TCF signaling, reflecting a novel pathophysiological step in tumorigenesis. They offer unique genomic strategies that could re-establish hormone expression in the context of canonical oncogenic mutations to reconstitute the GUYC2C axis and oppose transformation.
2022-01-03 | GSE171910 | GEO
Project description:The Wnt signaling pathway is involved in many differentiation events during embryonic development and can lead to tumor formation after aberrant activation of its components. ?-catenin, a cytoplasmic component, plays a major role in the transduction of the canonical wnt/ ?-catenin signaling. The aim of this study was to identify novel genes that are regulated by active ?-catenin/TCF signaling in hepatocellular carcinoma. We selected and expanded isogenic clones from hepatocellular carcinoma-derived Huh7 cells with high and low ?-catenin/TCF activities. We showed that, high TCF activity Huh7 cells lead to bigger and more aggressive tumors when xenografted into nude mice. We used SAGE (Serial Analysis of Gene Expression), genome-wide microarray and in silico promoter analysis in parallel, to compare gene expression between low (basal) and high (transfected) ?-catenin/TCF activity clones, those had been xenografted into nude mice. We compared and contrasted SAGE and genome-wide microarray data, in parallel. Finally; after combined analysis, we identified BRI3 and HSF2 as novel targets of Wnt/?-catenin signaling in hepatocellular carcinoma. High TCF activity Huh7 cell line (Huh7-S33Y) was compared to control Huh7 cell line (Huh7-Vec) by using 25 ug of total RNA isolated from each sample
2009-09-30 | E-GEOD-11912 | biostudies-arrayexpress
Project description:The forkhead box transcription factor FOXQ1 is aberrantly induced in various cancers, and contributes to tumour growth and metastasis. It has been suggested that the oncogenic potential of FOXQ1 may be explained by its activation of the Wnt/β-catenin signalling pathway.However, the mode of action of FOXQ1 in the Wnt pathway remains to be resolved. Here we report that FOXQ1 is bimodal transcriptional activator of Wnt target gene expression in normal and cancer cells. Using co-immunoprecipitation, proximity proteomics, and reporter assays, we show that FOXQ1 engages the Wnt transcriptional complex to promote gene expressionvia TCF/LEF transcription factors.
2022-10-05 | PXD030464 | Pride
Project description:The forkhead box transcription factor FOXQ1 is aberrantly induced in various cancers, and contributes to tumour growth and metastasis. It has been suggested that the oncogenic potential of FOXQ1 may be explained by its activation of the Wnt/β-catenin signalling pathway. However, the mode of action of FOXQ1 in the Wnt pathway remains to be resolved. Here we report that FOXQ1 is bimodal transcriptional regulator of Wnt target gene expression in normal and cancer cells. Using co-immunoprecipitation, proximity proteomics, and reporter assays, we show that FOXQ1 partly engages the Wnt transcriptional complex to promote gene expression via TCF/LEF transcription factors.
2022-10-05 | PXD035624 | Pride
Project description:The microarray gene expression analysis revealed that TCF-4 isoforms activate different downstream target genes in HCC. TCF-4J upregulated genes associated with Wnt/beta-catenin, Notch, and insulin/IGF-1/IRS1 signal transduction pathway. 1 HAK-1A HCC clone overexpressing TCF-4J, 1 HAK-1A HCC clone overexpressing TCF-4K
2013-11-01 | E-GEOD-42512 | biostudies-arrayexpress
Project description:The Wnt signaling pathway is involved in many differentiation events during embryonic development and can lead to tumor formation after aberrant activation of its components. Β-catenin, a cytoplasmic component, plays a major role in the transduction of the canonical wnt/ β-catenin signaling. The aim of this study was to identify novel genes that are regulated by active β-catenin/TCF signaling in hepatocellular carcinoma. We selected and expanded isogenic clones from hepatocellular carcinoma-derived Huh7 cells with high and low β-catenin/TCF activities. We showed that, high TCF activity Huh7 cells lead to bigger and more aggressive tumors when xenografted into nude mice. We used SAGE (Serial Analysis of Gene Expression), genome-wide microarray and in silico promoter analysis in parallel, to compare gene expression between low (basal) and high (transfected) β-catenin/TCF activity clones, those had been xenografted into nude mice. We compared and contrasted SAGE and genome-wide microarray data, in parallel. Finally; after combined analysis, we identified BRI3 and HSF2 as novel targets of Wnt/β-catenin signaling in hepatocellular carcinoma.
2009-09-30 | GSE11912 | GEO
Project description:The Wnt signaling pathway is involved in many differentiation events during embryonic development and can lead to tumor formation after aberrant activation of its components. Β-catenin, a cytoplasmic component, plays a major role in the transduction of the canonical wnt/ β-catenin signaling. The aim of this study was to identify novel genes that are regulated by active β-catenin/TCF signaling in hepatocellular carcinoma. We selected and expanded isogenic clones from hepatocellular carcinoma-derived Huh7 cells with high and low β-catenin/TCF activities. We showed that, high TCF activity Huh7 cells lead to bigger and more aggressive tumors when xenografted into nude mice. We used SAGE (Serial Analysis of Gene Expression), genome-wide microarray and in silico promoter analysis in parallel, to compare gene expression between low (basal) and high (transfected) β-catenin/TCF activity clones, those had been xenografted into nude mice. We compared and contrasted SAGE and genome-wide microarray data, in parallel. Finally; after combined analysis, we identified BRI3 and HSF2 as novel targets of Wnt/β-catenin signaling in hepatocellular carcinoma.
2009-09-30 | GSE11916 | GEO