Ontology highlight
ABSTRACT:
PROVIDER: PRJNA202069 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:LGR5 positivity defines stem-like cells in colorectal cancer [aCGH]
| PRJNA202103 | ENA
Project description:LGR5 positivity defines stem-like cells in colorectal cancer [Expression]
| PRJNA198024 | ENA
Project description:Mutations in APC or β-catenin that cause aberrant activation of Wnt signaling are responsible for the initiation of colorectal tumor development. LGR5 is specifically expressed in stem cells of the intestine, stomach and hair follicle, and plays essential roles in maintaining tissue homeostasis. LGR5-positive stem cells have been shown to be responsible for the intestinal adenoma initiated by some mutations in APC . Furthermore, it has recently been reported that Lgr5, which is associated with the Frizzled/Lrp Wnt receptor complex, interacts with R-spondins and thereby activates Wnt signaling. However, the function of LGR5 in colorectal tumorigenesis has been unclear. Here we show that LGR5 is required for the tumorigenicity of colorectal cancer cells. We also show that the transcription factor GATA6 directly enhances the expression of LGR5. DLD1 cells were infected with a lentivirus expressing an shRNA targeting GATA6 or LGR5.
2011-10-17 | E-GEOD-32987 | biostudies-arrayexpress
Project description:Metastasis is the leading cause of cancer-related mortality. Cancer stem cells contribute to metastasis in the murine colon cancer models, but the underlying mechanisms are unclear. Here we report a Wnt ligand, Dickkopf2 (DKK2) is essential for colorectal cancer stemness. Genetic depletion of Dkk2 in intestinal epithelial or stem cells reduced tumorigenesis as well as expression of the stem cell marker gene Lgr5 in a model of colitis-associated cancer. Mechanistically, DKK2 activates c-Src followed by increased LGR5 expressing stem cells in colorectal cancer through degradation of HNF4α1. Splenic injection of DKK2-deficient cancer organoids into C57BL/6 mice resulted in a significant reduction of liver metastases compared to the control cancer organoids in spite of the presence of oncogenic mutations in Apc, Kras and Tp53 genes. These findings suggest that DKK2 is required for stemness of colorectal cancer cells, which in turn contributes to metastasis.
2024-11-11 | GSE157529 | GEO
Project description:We analyzed gene expression of 3 lines LGR5-GFP, 2 lines KRT20-GFP knock-in colorectal tumor organdies. The cancer stem cell (CSC) theory highlights a self-renewing subpopulation of cancer cells that fuels tumour growth. The existence of human CSCs is mainly supported by xenotransplantation of prospectively isolated cells, but their clonal dynamics and plasticity remain unclear. Here, we show that human LGR5+ colorectal cancer cells serve as CSCs in growing cancer tissues. Lineage-tracing experiments with a tamoxifen inducible Cre knock-in allele of LGR5 reveal the self-renewal and differentiation capacity of LGR5+ tumour cells. Selective ablation of LGR5+ CSCs in LGR5-iCaspase9 knock-in organoids leads to tumour regression, followed by tumour regrowth driven by re-emerging LGR5+ CSCs. KRT20 knock-in reporter marks differentiated cancer cells that constantly diminish in tumour tissues, while reverting to LGR5+ CSCs and contributing to tumour regrowth after LGR5+ CSC ablation. We also show that combined chemotherapy potentiates LGR5+ CSCs targeting. These data provide insights into the plasticity of CSCs and their potential as a therapeutic target in human colorectal cancer.
2017-03-30 | GSE83513 | GEO
Project description:To further elucidate the role of the intestinal stem cell marker Leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) in colorectal cancer (CRC), we exposed Lgr5-EGFP-IRES-Cre-ERT2 mice to azoxymethane/dextrane sodium sulfate (AOM/DSS) which induces inflammation-driven colon tumors. Tumors were then flow-sorted into fractions of epithelial cells that expressed high or low levels of Lgr5 and were characterized using gene expression profiling. In the AOM/DSS-induced mouse colon tumors Lgr5 high cells showed higher levels of several stem cell-associated genes and higher Wnt signaling than Lgr5 low tumor cells and Lgr5 high normal colon epithelial cells. To further elucidate the role of the intestinal stem cell marker Leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) in colorectal cancer (CRC), we transduced SW480 CRC cells with lentiviral shRNA constructs to silence LGR5 expression. This resulted in a depletion of spheres but did not affect adherently growing cells. Spheres expressed higher levels of several stem cell-associated genes than adherent cells. Notch signaling was down-regulated upon LGR5 silencing. This was confirmed by immunohistochemistry against cleaved NOTCH1. Normal mouse colons and AOM/DSS-induced mouse colon tumors were flow-sorted into Lgr5 high and low cells before gene expression was measured. Fifteen independent experiments were performed using seven individual mice for normal colons and eight for tumors. Appropriate LGR5 status was confirmed by real-time qRT-PCR before measuring silencing induced gene expression. Three independent experiments were performed for each cell fraction using separately cultured cells for each experiment.
2013-04-19 | E-GEOD-46200 | biostudies-arrayexpress
Project description:Mutations in APC or β-catenin that cause aberrant activation of Wnt signaling are responsible for the initiation of colorectal tumor development. LGR5 is specifically expressed in stem cells of the intestine, stomach and hair follicle, and plays essential roles in maintaining tissue homeostasis. LGR5-positive stem cells have been shown to be responsible for the intestinal adenoma initiated by some mutations in APC . Furthermore, it has recently been reported that Lgr5, which is associated with the Frizzled/Lrp Wnt receptor complex, interacts with R-spondins and thereby activates Wnt signaling. However, the function of LGR5 in colorectal tumorigenesis has been unclear. Here we show that LGR5 is required for the tumorigenicity of colorectal cancer cells. We also show that the transcription factor GATA6 directly enhances the expression of LGR5.
2011-10-18 | GSE32987 | GEO
Project description:To further elucidate the role of the intestinal stem cell marker Leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) in colorectal cancer (CRC), we exposed Lgr5-EGFP-IRES-Cre-ERT2 mice to azoxymethane/dextrane sodium sulfate (AOM/DSS) which induces inflammation-driven colon tumors. Tumors were then flow-sorted into fractions of epithelial cells that expressed high or low levels of Lgr5 and were characterized using gene expression profiling. In the AOM/DSS-induced mouse colon tumors Lgr5 high cells showed higher levels of several stem cell-associated genes and higher Wnt signaling than Lgr5 low tumor cells and Lgr5 high normal colon epithelial cells. To further elucidate the role of the intestinal stem cell marker Leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) in colorectal cancer (CRC), we transduced SW480 CRC cells with lentiviral shRNA constructs to silence LGR5 expression. This resulted in a depletion of spheres but did not affect adherently growing cells. Spheres expressed higher levels of several stem cell-associated genes than adherent cells. Notch signaling was down-regulated upon LGR5 silencing. This was confirmed by immunohistochemistry against cleaved NOTCH1.
2013-04-19 | GSE46200 | GEO
Project description:Metastasis is the leading cause of cancer-related mortality. Cancer stem cells contribute to metastasis in the murine colon cancer models, but the underlying mechanisms are unclear. Here we report a Wnt ligand, Dickkopf2 (DKK2) is essential for colorectal cancer stemness. Genetic depletion of Dkk2 in intestinal epithelial or stem cells reduced tumorigenesis as well as expression of the stem cell marker gene Lgr5 in a model of colitis-associated cancer. Mechanistically, DKK2 activates c-Src followed by increased LGR5 expressing stem cells in colorectal cancer through degradation of HNF4α1. Splenic injection of DKK2-deficient cancer organoids into C57BL/6 mice resulted in a significant reduction of liver metastases compared to the control cancer organoids in spite of the presence of oncogenic mutations in Apc, Kras and Tp53 genes. These findings suggest that DKK2 is required for stemness of colorectal cancer cells, which in turn contributes to metastasis.
2021-09-01 | GSE157645 | GEO
Project description:Metastasis is the leading cause of cancer-related mortality. Cancer stem cells contribute to metastasis in the murine colon cancer models, but the underlying mechanisms are unclear. Here we report a Wnt ligand, Dickkopf2 (DKK2) is essential for colorectal cancer stemness. Genetic depletion of Dkk2 in intestinal epithelial or stem cells reduced tumorigenesis as well as expression of the stem cell marker gene Lgr5 in a model of colitis-associated cancer. Mechanistically, DKK2 activates c-Src followed by increased LGR5 expressing stem cells in colorectal cancer through degradation of HNF4α1. Splenic injection of DKK2-deficient cancer organoids into C57BL/6 mice resulted in a significant reduction of liver metastases compared to the control cancer organoids in spite of the presence of oncogenic mutations in Apc, Kras and Tp53 genes. These findings suggest that DKK2 is required for stemness of colorectal cancer cells, which in turn contributes to metastasis.
2024-11-11 | GSE157531 | GEO