Nox1 and Npy1r mark regional colon stem cell populations that serve as cancer origins in vivo [RNA-seq2]
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PROVIDER: PRJNA1295413 | ENA |
REPOSITORIES: ENA
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Project description:Current colorectal cancer (CRC) mouse models lack either colon specificity, limiting progression towards more advanced disease, or preclude evaluation of resident stem cells as cancer origins. Here, we report identification of Nox1 and Npy1r as cell-surface markers enriched in Lgr5+ stem cells predominantly within the caecum and exclusively within the mid-distal colorectum respectively. Selective dysregulation of Wnt signalling in Nox1+ or Npy1r+ stem cells using new CreERT2 mouse lines drives colon cancer initiation, predominantly within the caecum and the rectum respectively, establishing these stem cell populations as important sources of colon cancer. Selective conditional activation of Wnt signalling and oncogenic K-RAS in combination with loss of Trp53 in these stem cell compartments resulted in development of advanced, invasive cancers. This study establishes the new CreERT2 drivers as valuable tools for studying stem cell contributions to colon cancer.
2025-07-29 | GSE303433 | GEO
Project description:Current colorectal cancer (CRC) mouse models lack either colon specificity, limiting progression towards more advanced disease, or preclude evaluation of resident stem cells as cancer origins. Here, we report identification of Nox1 and Npy1r as cell-surface markers enriched in Lgr5+ stem cells predominantly within the caecum and exclusively within the mid-distal colorectum respectively. Selective dysregulation of Wnt signalling in Nox1+ or Npy1r+ stem cells using new CreERT2 mouse lines drives colon cancer initiation, predominantly within the caecum and the rectum respectively, establishing these stem cell populations as important sources of colon cancer. Selective conditional activation of Wnt signalling and oncogenic K-RAS in combination with loss of Trp53 in these stem cell compartments resulted in development of advanced, invasive cancers. This study establishes the new CreERT2 drivers as valuable tools for studying stem cell contributions to colon cancer.
2025-07-29 | GSE303434 | GEO
Project description:Current colorectal cancer (CRC) mouse models lack either colon specificity, limiting progression towards more advanced disease, or preclude evaluation of resident stem cells as cancer origins. Here, we report identification of Nox1 and Npy1r as cell-surface markers enriched in Lgr5+ stem cells predominantly within the caecum and exclusively within the mid-distal colorectum respectively. Selective dysregulation of Wnt signalling in Nox1+ or Npy1r+ stem cells using new CreERT2 mouse lines drives colon cancer initiation, predominantly within the caecum and the rectum respectively, establishing these stem cell populations as important sources of colon cancer. Selective conditional activation of Wnt signalling and oncogenic K-RAS in combination with loss of Trp53 in these stem cell compartments resulted in development of advanced, invasive cancers. This study establishes the new CreERT2 drivers as valuable tools for studying stem cell contributions to colon cancer.
2025-07-29 | GSE303295 | GEO
Project description:Nox1 and Npy1r mark regional colon stem cell populations that serve as cancer origins in vivo [scRNA_seq]
| PRJNA1295414 | ENA
Project description:Nox1 and Npy1r mark regional colon stem cell populations that serve as cancer origins in vivo [RNA_seq]
| PRJNA1294774 | ENA
Project description:Pancreatic Cancer (PC) is a highly metastatic malignancy. Over 80% of PC patients present with advanced-stage disease, preventing potentially curative surgery. The Neuropeptide Y (NPY)system, best known for its role in controling energy homeostasis, has also been show to promote tumorigenesis in a range of cancer types, but its role in PC has yet to be explored. Here, we show that expression of NPY and NPY1R are upregulated in mouse PC models and human PC patients. Moreover, using the genetically engineered, autochthonous KPR172HC mouse model of PC we demonstrate that pancreas-specific and whole-body knockout of Npy1r significantly decreases metastasis to the liver. We identify that treatment with the NPY1R antagonist BIBO330485 significantly reduces KPR172HC migratory capacity on cell-derived matrices. Importantly, pharmacological NPY1R inhibition in an intrasplenic model of PC metastasis recapitulated the results of our genetic studies, with BIBO3304 significantly decreasing metastasis in the liver. Together, our results reveal that NPY/NPY1R signaling is a novel anti-metastatic target in PC.
2025-05-07 | PXD058833 | Pride
Project description:NOX1 gene is member of the NADPH-dependent superoxide producing enzyme family. It generates reactive oxygen species (ROS) in regulated manner in response to growth factors, cytokines and calcium signal. Low levels of ROS play role in many processes including cell proliferation, inflammatory response and mitogenesis. NOX1 over-expression in colon cancer cell lines as well as surgical samples suggests a role in colon cancer. We identified unique target sequences of siRNAs for post-transcriptional silencing of NOX1. Gene specific and scrambled (control) sequence carrying U6 promoter/shRNA cassettes were cloned into GFP expression vector. Stable clones were selected based on NOX1 expression after transient transfection of HT-29 cells. Clone 6A and 6C showed 70-80% decrease in NOX1 expression. The cells were expanded and analyzed further. We measured decreased ROS production, cell proliferation and G1/S block of the cell cycle. HT-29 parental cells, clone SA (scrambled) and clone 6A (gene specific) were utilized to establish xenografts in athymic mice to investigate the effect of NOX1 silencing on tumor growth and gene expression in vivo. Significant decrease was measured in the volume of forming tumors. The stable clones and corresponding xenografts were analyzed on microarray. The microarray data was validated with real-time PCR and western-blot analysis demonstrating the inhibition of genes important in cell cycle regulation and angiogenesis. The results of this study show silencing NOX1 levels of generated ROS decreased, the tumor formation attenuated in vivo suggesting NOX1 may be a therapeutic target for colon cancer. Experiment Overall Design: We have found that NOX1 over-expression in colon cancer cell lines as well as surgical samples suggests a role in colon cancer. We identified unique target sequences of siRNAs for post-transcriptional silencing of NOX1. Gene specific and scrambled (control) sequences carrying the U6 promoter/shRNA cassettes were cloned into a GFP expression vector. Stable clones were selected based on NOX1 expression after transient transfection of HT-29 cells. HT-29 parental cells, clone SA (scrambled) and clone 6A (gene specific) were utilized to establish xenografts in athymic mice to investigate the effect of NOX1 silencing on tumor growth and gene expression in vivo. A significant decrease was measured in the volume of tumors formed. The stable clones and corresponding xenografts were analyzed on microarray. The microarray data was validated with real-time PCR and western-blot analysis demonstrating the inhibition of genes important in cell cycle regulation and angiogenesis. The results of this study show silencing NOX1 levels of generated ROS decreased, the tumor formation attenuated in vivo suggesting NOX1 may be a therapeutic target for colon cancer.
2008-06-13 | E-GEOD-4561 | biostudies-arrayexpress
Project description:Pancreatic Cancer (PC) is a highly metastatic malignancy. Over 80% of PC patients present with distant disease, preventing potentially curative surgery. The Neuropeptide Y (NPY) system, best known for its role in controlling energy homeostasis, has also been shown to promote tumorigenesis in a range of cancer types, but its role in PC has yet to be explored. Here, we show that expression of NPY and NPY1R are upregulated in mouse PC models and human PC patients. Moreover, using the genetically engineered, autochthonous KPR172HC mouse model of PC we demonstrate that pancreas-specific and whole-body knockout of Npy1r significantly decreases metastasis to the liver. We identify that treatment with the NPY1R antagonist BIBO3304 significantly reduces KPR172HC migratory capacity on cell-derived matrices. Importantly, pharmacological NPY1R inhibition in an intrasplenic model of PC metastasis recapitulated the results of our genetic studies, with BIBO3304 significantly decreasing metastasis in the liver. Together, our results reveal that NPY/NPY1R signaling is a novel anti-metastatic target in PC.
2025-03-19 | GSE283652 | GEO
Project description:The Sordaria macrospora nox1 mutant has a block in sexual development at the stage of protoperithecia formation, and therefore is sterile. The aim of this study was to determine the transcriptome of microdissected protoperithecia from the mutant, as well as the transcriptomes of total RNA from the mutant and the wild type for comparison. The data were then compared with transcriptome data from protoperithecia of the wild type and the developemental mutant pro1; the corresponding data were generated in a previous study (Teichert et al. 2012, BMC Genomics 13: 511, GEO accession GSE33668). The samples (amplified RNA from nox1 microdissected protoperithecia and total RNA from nox1 and wild type mycelia undergoing sexual development) were sequenced as paired-end reads on an Illumina HiSeq 2000, two independent biological replicates for each nox1 sample and one replicate for the wild type.
2014-03-10 | E-GEOD-49363 | biostudies-arrayexpress
Project description:NOX1 is a catalytic subunit of nonphagocytic NADPH oxidase, mainly localized to smooth muscle cells in the vasculature. We investigated the pathology underlying the pulmonary arterial hypertension-like phenotype demonstrated in mice deficient in the Nox1 gene (Nox1-KO). Spontaneous enlargement and hypertrophy of the right ventricle, accompanied by hypertrophy of pulmonary vessels, were demonstrated in Nox1-KO at 9-18 weeks of age. Since an increased number of α-smooth muscle actin-positive vessels was observed in Nox1-KO, pulmonary arterial smooth muscle cells (PASMCs) were isolated and characterized by flow cytometry and TUNEL staining. In Nox1-/Y PASMC, the number of apoptotic cells was significantly reduced without any change in the expression of endothelin-1, and hypoxia-inducible factors HIF-1a and HIF-2a, factors implicated in the pathogenesis of PAH. Transcriptional profiling of mouse pulmonary arterial smooth muscle cells in wild-type and NOX1-KO was analyzed.
2014-01-22 | GSE42014 | GEO