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

GSE157529 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 6 samples Submitted 2024/11/11 Platform GPL19057
Summary
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.
Published in
Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties
Shin JH, Park J, Lim J et al. · eLife 2024 · PMID 39535280 · doi:10.7554/eLife.97279
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Also filed as BioProject PRJNA661579 and SRA study SRP280160. Searching any of these in the dataset finder brings you back here.

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