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Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties

ABSTRACT: Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties

PROVIDER: PRJNA1162543 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30716163_1.fastq.gz	Fastqsanger.gz
	SRR30716163_2.fastq.gz	Fastqsanger.gz
	SRR30716164_1.fastq.gz	Fastqsanger.gz
	SRR30716164_2.fastq.gz	Fastqsanger.gz
	SRR30716165_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties

Project description:Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties

| PRJNA661575 | ENA

Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties

Project description:Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties

| PRJNA661579 | ENA

Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties [RNA-seq]

Project description:Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties [RNA-seq]

| PRJNA661581 | ENA

Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties

Project description:Metastasis is the leading cause of cancer-related mortality. Paneth cells provide stem cell niche factors in the homeostatic condition, but the underlying mechanisms of cancer stem cell niche development are unclear. Here we report that Dickkopf-2 (DKK2) is essential for Paneth-like cell generation during the metastasis of colon cancer. Splenic injection of DKK2-knockout (KO) 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 carcinogenic mutations in Apc, Kras and Tp53 genes. RNA-seq analysis of DKK2 KO organoids showed reduction of Paneth cell marker genes such as Lysozymes and Defensins. Ingenuity pathway analysis (IPA) of the RNA-seq data and assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) suggested HNF4A as a downstream target of DKK2. Chromatin immunoprecipitation followed by sequencing (Chip-seq) analysis showed that HNF4A binds to the open chromatin regions of Sox9, a well-known transcription factor for Paneth cell differentiation. Reduction of Paneth-like cells in the absence of DKK2 has been confirmed in the murine metastatic model of colon cancer using flow cytometry, immunohistochemistry and single cell RNA-seq. These data suggest the necessity of DKK2 in Paneth-like cell generation. Thus, DKK2 contributes to stem cell niche development during the metastatic progression of colon cancer.

2024-11-11 | GSE277510 | GEO

Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties.

Project description:Metastasis is the leading cause of cancer-related mortality. Paneth cells provide stem cell niche factors in homeostatic conditions, but the underlying mechanisms of cancer stem cell niche development are unclear. Here, we report that Dickkopf-2 (DKK2) is essential for the generation of cancer cells with Paneth cell properties during colon cancer metastasis. Splenic injection of Dkk2 knockout (KO) cancer organoids into C57BL/6 mice resulted in a significant reduction of liver metastases. Transcriptome analysis showed reduction of Paneth cell markers such as lysozymes in KO organoids. Single-cell RNA sequencing analyses of murine metastasized colon cancer cells and patient samples identified the presence of lysozyme positive cells with Paneth cell properties including enhanced glycolysis. Further analyses of transcriptome and chromatin accessibility suggested hepatocyte nuclear factor 4 alpha (HNF4A) as a downstream target of DKK2. Chromatin immunoprecipitation followed by sequencing analysis revealed that HNF4A binds to the promoter region of Sox9, a well-known transcription factor for Paneth cell differentiation. In the liver metastatic foci, DKK2 knockout rescued HNF4A protein levels followed by reduction of lysozyme positive cancer cells. Taken together, DKK2-mediated reduction of HNF4A protein promotes the generation of lysozyme positive cancer cells with Paneth cell properties in the metastasized colon cancers.

| S-EPMC11560131 | biostudies-literature

Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties

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

Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties [RNA-seq]

2024-11-11 | GSE157531 | GEO

Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-11-11 | GSE157535 | GEO

Control of Paneth cell fate, intestinal inflammation and tumorigenesis by PKCλ/ι

Project description:Paneth cells are a highly specialized population of intestinal epithelial cells located in the crypt adjacent to Lgr5+ stem cells, from which they differentiate through a process that requires downregulation of the Notch pathway. Their ability to store and release antimicrobial peptides protects the host from intestinal pathogens and controls intestinal inflammation. Here we show that PKCλ/ι is required for Paneth cell differentiation at the level of Atoh1 and Gfi1, through the control of EZH2 stability by direct phosphorylation. The selective inactivation of PKCλ/ι in epithelial cells results in the loss of mature Paneth cells, increased apoptosis and inflammation, and enhanced tumorigenesis. Importantly, PKCλ/ι expression in human Paneth cells decreases with progression of Crohn's disease. Kaplan-Meier survival analysis of CRC patients revealed that low PRKCI levels correlated with significantly worse patient survival. Therefore, PKCλ/ι is a negative regulator of intestinal inflammation and cancer through its role in Paneth cell homeostasis.

2017-08-23 | GSE84118 | GEO

Paneth cells

Project description:Paneth cells

| PRJNA994579 | ENA