Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA92757 | ENA |
REPOSITORIES: ENA
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Project description:Our goal was to assess gene expression changes that occur when Lymphoid Enhancer Factor-1 (LEF-1) promotes epithelial-mesenchymal transition (EMT), the primary mechanism of tumor metastasis. To observe this phenomenon without interference from other signaling pathways, we selected DLD1 colon carcinoma cells (ATCC) which contain a mutation in APC. APC is a necessary component of a ubiquitin protein complex (including GSK-3beta, Axin, etc.) that is responsible for degrading cytoplasmic beta-catenin. Therefore, sufficient levels of LEF-1 can be easily activated by forming complexes with the abundant beta-catenin located in the cytoplasm of DLD1 cells. These complexes can then promote transcription of genes that stimulate EMT. We treated DLD1 cells with an adenoviral LEF-1 expression construct, which induced EMT within 48 hours. RNA was then extracted from these cells along with untreated DLD1 cells, then subjected to microarray analysis. From this analysis, we acquired several gene expression profiles by which epithelial colon carcinoma cells transform to an invasive, mesenchymal phenotype to initiate metastasis. Keywords: epithelial-mesenchymal transition, tumor metastasis, cancer progression, epithelial cell plasticity
2006-06-01 | GSE3229 | GEO
Project description:Our goal was to assess gene expression changes that occur when Lymphoid Enhancer Factor-1 (LEF-1) promotes epithelial-mesenchymal transition (EMT), the primary mechanism of tumor metastasis. To observe this phenomenon without interference from other signaling pathways, we selected DLD1 colon carcinoma cells (ATCC) which contain a mutation in APC. APC is a necessary component of a ubiquitin protein complex (including GSK-3beta, Axin, etc.) that is responsible for degrading cytoplasmic beta-catenin. Therefore, sufficient levels of LEF-1 can be easily activated by forming complexes with the abundant beta-catenin located in the cytoplasm of DLD1 cells. These complexes can then promote transcription of genes that stimulate EMT. We treated DLD1 cells with an adenoviral LEF-1 expression construct, which induced EMT within 48 hours. RNA was then extracted from these cells along with untreated DLD1 cells, then subjected to microarray analysis. From this analysis, we acquired several gene expression profiles by which epithelial colon carcinoma cells transform to an invasive, mesenchymal phenotype to initiate metastasis. Experiment Overall Design: DLD1 cells were treated with an adenoviral LEF-1 expression construct as described by Kim et al. (2002). Total RNA was extracted from both untreated and treated DLD1 cells using the RNeasy mini extraction kit (Qaigen). RNA amplification, biotin labeling, microarray hybridization, and fluidics were performed following the eukaryotic sample and array processing protocol (Affymetrix). Chips were scanned using an Affymetrix Gene Array Scanner (Hewlett-Packard). Raw data was compiled using Microarray Suite 5.0 software (Affymetrix).
2008-06-12 | E-GEOD-3229 | biostudies-arrayexpress
Project description:To validate the suitability of two commonly used colorectal cancer cell lines, DLD1 and SW480, as model systems to study colorectal carcinogenesis, we treated these cell lines with beta-catenin siRNA and identified beta-catenin target genes using DNA microarrays. The list of identified target genes was compared to previously published beta-catenin target genes found in the PubMed and the GEO databases. Based on the large number of beta-catenin target genes found to be similarly regulated in DLD1, SW480 and LS174T as well as the large overlap with confirmed β-catenin target genes, we conclude that DLD1 and SW480 colon carcinoma cell lines are suitable model systems to study beta-catenin regulated genes and signaling pathways 12 arrays (2 cell lines, 2 treatments, 3 biological replicates)
2013-12-31 | E-GEOD-44097 | biostudies-arrayexpress
Project description:To validate the suitability of two commonly used colorectal cancer cell lines, DLD1 and SW480, as model systems to study colorectal carcinogenesis, we treated these cell lines with β-catenin siRNA and identified β-catenin target genes using DNA microarrays. The list of identified target genes was compared to previously published β-catenin target genes found in the PubMed and the GEO databases. Based on the large number of β-catenin target genes found to be similarly regulated in DLD1, SW480 and LS174T as well as the large overlap with confirmed β-catenin target genes, we conclude that DLD1 and SW480 colon carcinoma cell lines are suitable model systems to study β-catenin regulated genes and signaling pathways
2013-12-31 | GSE44097 | GEO
Project description:Colorectal cancer (CRC) ranks second in cancer-related mortality worldwide, with clinical intractability and chemoresistance representing significant challenges driven by cancer stem cells (CSCs). Wnt/β-catenin signaling is a lynchpin of CSC self-renewal, but targetable upstream drivers remain elusive. Using bioinformatics we identified the proteoglycan SPOCK1 as a Wnt-associated CSC target. Critically, high SPOCK1 expression predicted poor patient prognosis and reduced progression-free survival following first-line chemotherapy. In vitro assays demonstrated that SPOCK1 levels modulated Wnt/β-catenin activity. SPOCK1 silencing inhibited β-catenin nuclear translocation and TCF/LEF-mediated transcription, which concurrently suppressed CRC proliferation and stemness. Conversely, SPOCK1 overexpression promoted β-catenin nuclear translocation and TCF/LEF-mediated transcription, which enhanced CRC proliferation and stemness. This SPOCK1-driven pro-tumorigenic effect was significantly reversed by the β-catenin/TCF/LEF inhibitor iCRT3, demonstrating SPOCK1’s dependence on Wnt transcriptional activation. The functional role was validated in vivo using a SPOCK1-overexpressing xenograft model and ex vivo using patient-derived organoids (PDOs), both confirming increased growth and β-catenin nuclear localization. Furthermore, data-independent acquisition (DIA) mass spectrometry of SPOCK1-overexpressing tumors revealed pro-tumorigenic signaling including c-Myc activity, oxidative phosphorylation, epithelial-mesenchymal transition. Notably, SPOCK1 drove remodeling of the tumor microenvironment, characterized by desmoplasia and fibrosis. Overall, our findings establish a SPOCK1/Wnt/β-catenin axis as a novel mechanism driving CRC tumorigenesis and stemness, positioning it as a promising therapeutic target to overcome Wnt-mediated progression and resistance.
2025-10-10 | GSE309532 | GEO
Project description:Deregulation of canonical Wnt/beta-catenin pathway is one of the earliest events in the pathogenesis of colon cancer. Mutations in APC or CTNNB1 (beta-catenin gene) are highly frequent in colon cancer and cause aberrant stabilization of b-catenin, which activates the transcription of Wnt target genes by binding to chromatin via the TCF/LEF transcription factors. Here we report an integrative analysis of genome-wide chromatin occupancy of b-catenin by chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) and gene expression profiling by microarray analysis upon RNAi-mediated knockdown of beta-catenin in colon cancer cells (GSE53656). Immunoprecipitated samples from human colon cancer SW480 cells with antibodies against beta-catenin and control IgG respectively were used for ChIP-seq experiments.
2014-03-12 | E-GEOD-53927 | biostudies-arrayexpress
Project description:We established a model system in human DLD1 colon cancer cells to study the transcriptional crosstalk between FOXO3A and beta-Catenin. Thereby, translocation to the nucleus of a AKT-insensitive mutant (T32A, S253A, S315A) of human FOXO3A fused to the ligand binding domain of human estrogen receptor can be induced by exposure to 4-hydroxy-tamoxifen. Furthermore, expression of a stable mutant (S33Y) of human beta-catenin is doxycycline inducible. Addition of those drugs separately or in combination allows identification of common or excusive target gene sets.
2012-05-01 | E-MEXP-3262 | biostudies-arrayexpress
Project description:Constitutive activation of Wnt/β-catenin signaling drives tumor initiation, maintenance, and metastasis in numerous preclinical models. Within the nucleus, β-catenin interacts with transcription factors of the TCF/LEF (T cell factor/lymphoid enhancer factor, TCFs) family. The transcriptional program mediated by these β-catenin/TCF interactions promotes cell proliferation, epithelial-mesenchymal transition (EMT), and a cancer stem-cell phenotype. COLO320DM is a human colorectal cancer line with an activated Wnt/ β-catenin pathway driven by an APC mutation. Here, we apply a doxycycline-inducible shRNA to knockdown (KD) CTNNB1 (encoding β-catenin) and study the impact on the global transcriptome of COLO320DM. We also design and express an shRNA-resistant rescue cDNA to rule out any potential off-target effect. The results reveal a global gene expression change upon CTNNB1-KD that is consistent with β-catenin’s role in serving as a signal hub downstream of the canonical Wnt pathway.
2025-10-21 | GSE216381 | GEO
Project description:Wnt/β-catenin signaling is a highly conserved molecular pathway that plays a crucial role in stem/progenitor systems and cancer. β-catenin, the main Wnt pathway effector, has two pools within a cell: one for cell-cell adhesion at the membrane and the other for transcriptional functions in the nucleus. However, the mechanism by which β-catenin mediates both roles remain unclear. The tightly controlled, well characterized system of nephrogenesis is an ideal model to decouple the roles of β-catenin at the membrane and in the nucleus. In kidney development, a delicate balance of nephron progenitor cell self-renewal and differentiation is required for the mesenchymal to epithelial transition (MET) in nephrogenesis and is driven by Wnt/β-catenin signaling. Given an ability to isolate and manipulate large numbers of NPCs in tissue culture, we can dissect the dual nature of β-catenin as a transcriptional activator and component of a cell membrane complex in adhesion. We pioneered a method using CRISPR/Cas9 gene editing to rapidly remove β-catenin, Tcf/Lef factors and simultaneous cadherin genes in primary NPCs. We have characterized the effects of modulating β-catenin and integrated RNA-seq results from β-catenin’s removal with mouse ChIP-seq and mouse single cell RNA -seq data. Functional analysis of β-catenin removal provides strong evidence for β-catenin regulation of NPC proliferation, independent of a direct Lef/Tcf associated transcriptional program. Together these data suggest β-catenin mediates aggregation, the first step in MET, through β-catenin mediated cell adhesion complexes while simultaneous transcriptional activation within these structures initiates the nephrogenic program. The studies provide new insight into the direct transcriptional role of Lef/Tcf/β-catenin complexes associated with the initiation of a nephron forming program. Overall, this study enhances an understanding of the molecular mechanisms underlying kidney development and the dual nature of β-catenin stem/progenitor systems at large.
2024-07-29 | GSE231753 | GEO
Project description:Deregulation of canonical Wnt/beta-catenin pathway is one of the earliest events in the pathogenesis of colon cancer. Mutations in APC or CTNNB1 (beta-catenin gene) are highly frequent in colon cancer and cause aberrant stabilization of b-catenin, which activates the transcription of Wnt target genes by binding to chromatin via the TCF/LEF transcription factors. Here we report an integrative analysis of genome-wide chromatin occupancy of b-catenin by chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) and gene expression profiling by microarray analysis upon RNAi-mediated knockdown of beta-catenin in colon cancer cells (GSE53656).
2014-03-12 | GSE53927 | GEO