Expression data from TOP-GFP sorted colon cancer cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE32408 | GEO | 2012/02/16
SECONDARY ACCESSION(S): PRJNA146385
REPOSITORIES: GEO
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Project description:Colon cancers typically contain tumor cell populations with differential WNT signaling activity. Colon cancer cells with high WNT-activity have been attributed increase tumorigenic potential and stem cell characteristics. We extracted tumor cells with differential WNT activity using fluorescent reporters from xenografted human colon cancer cell line tumors and primary human colon cancer xenografts and analysed their gene expression profiles. Colon cancer cell lines and primary colon cancer xenografts were transduced with lentiviral TOP-GFP reporters, and grown as xenografts in NOD-SCID mice. We disaggregated these tumors, flow sorted for GFPhigh and GFPlow tumor cells and subjected these populations to gene expression profiling.
2012-02-16 | E-GEOD-32408 | biostudies-arrayexpress
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2015-02-12 | E-GEOD-65879 | biostudies-arrayexpress
Project description:To analyze whether Wnt inhibitors LF3 and ICG-001 have similar influence on the gene expression of mouse salivary gland cancer stem cells Wnt/β-catenin signaling is a system that is essential for embryogenesis and tissue homeostasis which has been highly conserved through evolution. A deregulation of Wnt/β-catenin signals can initiate and promote human cancers, specifically of the colon, head and neck. As such, Wnt/β-catenin signaling represents an attractive target for cancer therapy. So far, however, no rationally developed compound targeting Wnt signaling has found clinical use. The interaction between β-catenin and TCF4 is necessary in the transduction of the signal; here we performed a High-Throughput-Screening (HTS) using AlphaScreen and ELISA techniques to identify small molecules that specifically disrupt this interaction. We identified compound LF3, a 4-thioureido-benzenesulfonamide derivative, as a robust inhibitor of β-catenin/TCF4 interactions and thus a good starting point for drug discovery, as suggested by Lipinski's “rule of five.” LF3 inhibited Wnt/β-catenin signaling in cells with exogenous reporters and in colon cancer cells with endogenously high Wnt activity. Medicinal chemistry identified an essential core structure and residues that could not be modified in LF3. Compound LF3 inhibited a number of features of cancer cells related to Wnt signaling, including high cell motility in Boyden chamber assays, hyperproliferation through induction of cell cycle arrest at the G1 phase, and the overexpression of key Wnt target genes. LF3 does not cause apoptosis or cell death or interfere with cadherin-mediated cell-cell adhesion. Remarkably, the self-renewal capacity of cancer stem cells was blocked by LF3 in concentration-dependent manners, as demonstrated by examination of sphere formation of colon and head and neck cancer stem cells in serum-free, non-attached conditions. LF3 also reduced tumor growth and induced differentiation in colon tumors in mouse xenografts. LF3 is thus a specific inhibitor of canonical Wnt signaling with a significant potential for further development for preclinical and clinical studies in cancer treatment.
2015-10-06 | GSE73732 | GEO
Project description:This study investigates the correlation between gene overexpression and resistance to apoptosis and hyper-proliferative phenotype in colorectal cancer. We analyzed the transcriptome of a cohort of xenografted colorectal tumors and primary resected biopsies together with normal tissue datasets and identified a set of genes overexpressed in colon cancer. KEYWORDS: transcription-profile, colon, colon-cancer, xenograft
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Project description:Estrogens are well known steroid hormones necessary to maintain bone health. In addition, mechanical loading, which estrogen signaling may intersect with the Wnt/β-catenin pathway, is also essential for bone health. As osteocytes are known as the major mechanosensory cells embedded in mineralized bone matrix, osteocyte ERα deletion mice (ERαΔOcy/ΔOcy) were generated by mating ERα floxed mice with Dmp1-Cre mice to determine functions of ERα in osteocytes. Trabecular bone mineral density of female, but not male ERαΔOcy/ΔOcy mice was significantly decreased. Bone formation parameters in ERαΔOcy/ΔOcy were significantly decreased while osteoclast parameters were unchanged. This suggests that ERα in osteocytes exerts osteoprotective function by positively controlling bone formation. To identify potential targets of ERα, gene array analysis of Dmp1-GFP osteocytes FACS sorted from ERαΔOcy/ΔOcy and control mice was performed. Expression of Mdk and Sostdc1, both known inhibitors of Wnt, were significantly increased without alteration of the mature osteocyte marker Sost or β-catenin. Hindlimb unloading exacerbated the trabecular bone loss, but surprisingly cortical bone was resistant. These studies show that ERα in osteocytes has osteoprotective effects in trabecular bone through regulating expression of Wnt antagonists, but conversely plays a negative role in cortical bone loss due to unloading.
2013-12-12 | GSE41997 | GEO
Project description:Estrogens are well known steroid hormones necessary to maintain bone health. In addition, mechanical loading, which estrogen signaling may intersect with the Wnt/β-catenin pathway, is also essential for bone health. As osteocytes are known as the major mechanosensory cells embedded in mineralized bone matrix, osteocyte ERα deletion mice (ERαÎOcy/ÎOcy) were generated by mating ERα floxed mice with Dmp1-Cre mice to determine functions of ERα in osteocytes. Trabecular bone mineral density of female, but not male ERαÎOcy/ÎOcy mice was significantly decreased. Bone formation parameters in ERαÎOcy/ÎOcy were significantly decreased while osteoclast parameters were unchanged. This suggests that ERα in osteocytes exerts osteoprotective function by positively controlling bone formation. To identify potential targets of ERα, gene array analysis of Dmp1-GFP osteocytes FACS sorted from ERαÎOcy/ÎOcy and control mice was performed. Expression of Mdk and Sostdc1, both known inhibitors of Wnt, were significantly increased without alteration of the mature osteocyte marker Sost or β-catenin. Hindlimb unloading exacerbated the trabecular bone loss, but surprisingly cortical bone was resistant. These studies show that ERα in osteocytes has osteoprotective effects in trabecular bone through regulating expression of Wnt antagonists, but conversely plays a negative role in cortical bone loss due to unloading. Wild type and osteocyte-specific Estrogen Receptor alpha knock-out mice were generated. The number of both genotypes of mice was three. Calvarial osteocytes of both genotypes harboring Dmp1-GFP were extracted by sequential enzymatic digestion, followed by FACS Aria sorting and total RNAs were purified for Affymetix GeneChip microarray analysis without pooling.
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Project description:Colon cancer is initiated by stem cells that escape the strict control. In most colon tumors this process is driven through aberrant activation of Wnt signaling by mutations that occur in components acting downstream of the receptor complex and that unfetter tumor cells from the need for Wnt ligands. Here we describe a special type of colon cancer that does not depend on mutated core components of the Wnt pathway. Genetically blocking Wnt secretion from epithelial cells of such tumors results in apoptosis, reduced expression of colon cancer markers, followed by enhanced tumor differentiation. In contrast to the normal colonic epithelium, such tumor cells auto-secrete Wnt ligands to maintain their uncontrolled proliferative behavior. In humans, we determined certain cases of colon cancers in which the Wnt pathway is hyperactive, but not through mutations in its core components. Our findings illuminate the path in therapy to find further subtypes of Wnt- dependent colon cancer, that might be responsive to Wnt secretion inhibitors.
2021-09-01 | GSE181738 | GEO
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
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