RNAseq of murine small intestinal tissue following epithelium-specific deletion of Bcl9/9l +/- Apc +/- mutant B-catenin
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB30780 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The aim of this experiment was to determine the contribution that components of the Wnt enhancesome (Bcl9/9l) make to Wnt driven intestinal transcriptional programmes in the context of normal intestinal homeostasis, or intestinal transformation driven by Apc depletion or B-catenin mutation.
2019-01-15 | E-MTAB-7546 | biostudies-arrayexpress
Project description:Bcl9 and Pygo function within the Wnt enhanceosome to effect β-catenin-dependent transcription. Whether they also mediate β-catenin-dependent neoplasia is unclear. Here we assess their roles in intestinal tumorigenesis initiated by Apc loss-of-function (ApcMin). Gene expression profiling revealed that loss-of-Bcl9 synergizes with loss-of-Pygo to shift gene expression within Apc-mutant adenomas from stem cell-like to differentiation along Notch-regulated secretory lineages.
2018-12-31 | GSE121130 | 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:Stabilized Alpha-Helix peptides of BCL9 HD2 (SAH-BCL9) block BCL9 and B9L interactions with beta-catenin and specifically downregulate Wnt target gene expression.
2012-08-23 | GSE33143 | GEO
Project description:We isolated ca. 500 forelimbs at 10 days post coitum, and performed ChIP-seq using anti-Bcl9 antibodies. Bcl9 is a beta-catenin transcriptional cofactor, therefore it allows the identification of binding sites of the canonical Wnt signalling-dependent transcriptional complex. This experiment allowed to define that, in this developmental context, Bcl9 acts as a beta-catenin dedicated partner. Moreover, it established a series of genome-wide Bcl9 (therefore Wnt/beta-catenin) tissue-specific target loci, thereby assessing the genetic relationship existing between Wnt signaling and other signalling cascades (e.g. the Bmp pathway).
2019-02-21 | E-MTAB-7652 | biostudies-arrayexpress
Project description:Stabilized Alpha-Helix peptides of BCL9 HD2 (SAH-BCL9) block BCL9 and B9L interactions with beta-catenin and specifically downregulate Wnt target gene expression. RNA from triplicate SAH-BCL9B- and vehicle-treated DLD1 samples (10 µM each for 12 hours) was hybridized to Affymetrix Human U133 Plus 2.0 arrays to asses global gene expression changes.
2012-08-23 | E-GEOD-33143 | biostudies-arrayexpress
Project description:Bcl9 and Bcl9l (Bcl9l) are commonly thought as beta-catenin-dependent Wnt signaling transcriptional activators. Here we searched for BCL9 interacts that could explain the PYGO-independent phenotype induced be the loss of the HD1 (PYGO-binding) domain of BCL9
2020-08-10 | PXD018805 | Pride
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.
2015-11-08 | GSE60837 | GEO
Project description:Summary: We studied how the binding of beta-catenin to the transcriptional coactivators B-cell CLL/lymphoma 9 (Bcl9) and Bcl9-Like (Bcl9L) affected mammary gland carcinogenesis in the MMTV-PyMT transgenic mouse model of metastatic breast cancer. Conditional knockout of both Bcl9 and Bcl9L resulted into tumor cell death. In contrast, disrupting the interaction of Bcl9/Bcl9L with beta-catenin, either by deletion of their HD2 domains or by a point mutation in the N-terminal domain of beta-catenin (D164A), diminished primary tumor growth and tumor cell proliferation and reduced tumor cell invasion and lung metastasis. In comparison, the effect of disrupting the HD1 domain-mediated binding of Bcl9/Bcl9L to Pygopus was more moderate. Interfering with the beta-catenin - Bcl9/Bcl9L - Pygo chain of adaptors only partially impaired the transcriptional response of mammary tumor cells to Wnt3a and TGF-beta treatment. The results indicate that Bcl9/Bcl9L critically enforce canonical Wnt signaling in its contribution to breast cancer growth and malignant progression.
2021-08-20 | GSE182404 | GEO
Project description:HCT116 colorectal cancer cells were treated with a novel inhibitor of ß-catenin/BCL9 interaction and evaluated for transcriptional changes using RNA-seq.
2022-01-01 | GSE182086 | GEO