Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA235259 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Wnt/β-catenin signaling mediates resistance of colorectal cancer cells to chemoradiotherapy
| PRJNA382241 | ENA
Project description:To identify Wnt target genes whose expression is differentially modulated by butyrate Doxycycline inducible DN-Tcf4 expression was used to repress Wnt signaling, cells were treated with butyrate or mock treated. Genes differentially regulated by butyrate in the absence of doxycycline but not in its presence (> 2 -fold, P < 0.01) were evaluated.
2014-01-16 | E-GEOD-54127 | biostudies-arrayexpress
Project description:Genetic and epigenetic defects in Wnt/ß-catenin signaling play important roles in colorectal cancer progression. Here we identify DACT3, a member of the DACT (Dpr/Frodo) gene family, as a negative regulator of Wnt/ß-catenin signaling that is transcriptionally repressed in colorectal cancer. Unlike other Wnt signaling inhibitors that are silenced by DNA methylation, DACT3 repression is associated with bivalent histone modifications. Remarkably, DACT3 expression can be robustly de-repressed by a pharmacological combination that simultaneously targets both histone methylation and deacetylation, leading to strong inhibition of Dishevelled (Dvl)-mediated Wnt/ß-catenin signaling and massive apoptosis of colorectal cancer cells. Our study identifies DACT3 as an important regulator of Wnt/ß-catenin signaling in colorectal cancer and suggests a potential strategy for therapeutic control of Wnt/ß-catenin signaling in colorectal cancer. Keywords: Colon cancer cell line
2008-03-29 | GSE10952 | GEO
Project description:Genetic and epigenetic defects in Wnt/?-catenin signaling play important roles in colorectal cancer progression. Here we identify DACT3, a member of the DACT (Dpr/Frodo) gene family, as a negative regulator of Wnt/ß-catenin signaling that is transcriptionally repressed in colorectal cancer. Unlike other Wnt signaling inhibitors that are silenced by DNA methylation, DACT3 repression is associated with bivalent histone modifications. Remarkably, DACT3 expression can be robustly de-repressed by a pharmacological combination that simultaneously targets both histone methylation and deacetylation, leading to strong inhibition of Dishevelled (Dvl)-mediated Wnt/?-catenin signaling and massive apoptosis of colorectal cancer cells. Our study identifies DACT3 as an important regulator of Wnt/ß-catenin signaling in colorectal cancer and suggests a potential strategy for therapeutic control of Wnt/ß-catenin signaling in colorectal cancer. This SuperSeries is composed of the SubSeries listed below.
2008-03-29 | GSE10972 | GEO
Project description:24 colon normal and tumor pairs using Illumina BeadChip Human Ref8-v2. Genetic and epigenetic defects in Wnt/ß-catenin signaling play important roles in colorectal cancer progression. Here we identify DACT3, a member of the DACT (Dpr/Frodo) gene family, as a negative regulator of Wnt/ß-catenin signaling that is transcriptionally repressed in colorectal cancer. Unlike other Wnt signaling inhibitors that are silenced by DNA methylation, DACT3 repression is associated with bivalent histone modifications. Remarkably, DACT3 expression can be robustly de-repressed by a pharmacological combination that simultaneously targets both histone methylation and deacetylation, leading to strong inhibition of Dishevelled (Dvl)-mediated Wnt/ß-catenin signaling and massive apoptosis of colorectal cancer cells. Our study identifies DACT3 as an important regulator of Wnt/ß-catenin signaling in colorectal cancer and suggests a potential strategy for therapeutic control of Wnt/ß-catenin signaling in colorectal cancer. The clinical information for the colon tumor is not available. Keywords: human colon tumor
2008-03-29 | GSE10950 | GEO
Project description:Analysis of colorectal cancer (CRC) cell line HT-29 treated with Sodium Butyrate. Sodium Butyrate, a HDAC inhibitor present in gut, can differentiate the undifferentiated HT-29 to enterocytes by the induction of brush border enzyme alkaline phosphatase. Results provide the transcriptional profiling underlying the butyrate-induced differentiation of CRC.
2016-12-31 | GSE61429 | GEO
Project description:But4ManNAc - an analog of ManNAc, the committed precursor of sialic acid - decreases metastatic potential, inhibits growth, and triggers apoptosis in many cancer cells. The anti-tumor effects of But4ManNAc may result from a synergistic interaction between butyrate-induced changes in gene expression and ManNAc-induced altered sialylation. This experiment provides insight into synergistic interactions by identifying changes in gene expression specific to But4ManNAc and not shared with butyrate.
2011-06-14 | GSE29922 | GEO
Project description:Canonical Wnt signaling output is mediated by β-catenin, which interacts with LEF/TCF transcription factors and recruits a general transcriptional activation complex to its C-terminus. Its N-terminus binds BCL9/9L proteins, which bind co-activators that in mammals contribute to fine-tuning the transcriptional output. We found that a BCL9/9L-dependent gene expression signature was strongly associated with patient outcome in colorectal cancer and that stem cell and mesenchymal genes determine its prognostic value. Abrogating BCL9/9L-β-catenin signaling in independent mouse colorectal cancer models resulted in virtual loss of these traits, and oncogenic intestinal organoids lacking BCL9/9L proteins proved no longer tumorigenic. Our findings suggest that the BCL9/9L arm of Wnt-β-catenin signaling sustains a stemness-to-differentiation equilibrium in colorectal cancer, which critically affects disease outcome. Mutational activation of the Wnt pathway is a key oncogenic event in colorectal cancer. Targeting the pathway downstream of activating mutations is challenging, and the therapeutic window is limited by intestinal toxicity. Contrasting with phenotypes caused by inactivating key Wnt pathway components, ablation of BCL9/9L proteins in adult mice indicated that they were dispensable for intestinal homeostasis, consistent with their role in tuning transcription. Cancer stem cells are increasingly recognized as responsible for tumor recurrence. The correlation between stemness traits in colorectal cancer models and BCL9/9L-β-catenin signaling suggests that high Wnt signaling output is required for their maintenance. Our findings suggest that pruning Wnt-β-catenin signaling might be well tolerated and prove sufficient for trimming stemness traits and improving disease outcome. Examination of Bcl9/9l-knockout versus wild-type transcriptome in murine AOM-DSS tumors, APC-Kras tumors and healthy colocyte extracts.
2015-11-08 | E-GEOD-60837 | biostudies-arrayexpress
Project description:Strong activation of the oncogenic Wnt/beta-catenin pathway is a main mechanism of resistance to FOXO3a-induced apoptosis promoted by PI3K and AKT inhibitors in colorectal cancer (CRC). Reducing Wnt/beta-catenin activity would sensitize colorectal tumors to these inhibitors. However, no Wnt/beta-catenin signaling inhibitor has proven clinical potential yet. Recently, inhibitors that block tankyrases were shown to reduce colon cancer cell proliferation by decreasing nuclear beta-catenin. We aim to identify determinants of response to these novel Wnt-inhibitors. Therefore, we treated in vivo three different patient-derived xenograft models (PDX; P2, P5 and P30) growing subcutaneously in NOD SCID mice with the novel tankyrase inhibitor NVP-TNKS656.
2015-08-10 | E-MTAB-2446 | biostudies-arrayexpress
Project description:But4ManNAc - an analog of ManNAc, the committed precursor of sialic acid - decreases metastatic potential, inhibits growth, and triggers apoptosis in many cancer cells. The anti-tumor effects of But4ManNAc may result from a synergistic interaction between butyrate-induced changes in gene expression and ManNAc-induced altered sialylation. This experiment provides insight into synergistic interactions by identifying changes in gene expression specific to But4ManNAc and not shared with butyrate. Specifically, microarrays will compare gene expression of metastatic breast cancer cells (MDA-MB-231) treated with But4ManNAc to that of cells treated with sodium butyrate at concentrations which inhibit invasiveness but do not trigger apoptosis. Differences in gene expression demonstrate a synergistic interaction between butyrate and sialylation as well as suggest mechanisms to account for this synergy. RNA preparations of treated and control metastatic breast cancer MDA-MB-231 cells were sent to Microarray Core (E). Five conditions where sent: cells treated with 50uM But4ManNAc, 125uM But4ManNAc, 50uM But5Man, 125uM But5Man, and Ethanol (control). Three replicate samples from each condition were used in the study. The RNA was amplified, labeled, and hybridized to the GLYCOv3 microarrays. Data was analyzed to identify differences in gene expression that demonstrate a synergistic interaction between butyrate and sialylation, as well as suggest mechanisms to account for this synergy.
2011-06-14 | E-GEOD-29922 | biostudies-arrayexpress