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wie-die-auc-bewertung-die-tatsächliche-leistung-von-modellen-unterschätzen-kann

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機密の逆因果説明を利用したナレッジ-ディスティレーション-ベースのモデル抽出攻撃

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Dickkopf-2 (DKK2) is essential for the generation of colon cancer cells exhibiting Paneth cell properties, which form a cancer stem cell niche to facilitate metastatic tumor growth.


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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.

### Competing Interest Statement

The authors have declared no competing interest.

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

dickkopf-2-promotes-the-generation-of-colon-cancer-cells-with-paneth-cell-properties-to-drive-metastasis


Dickkopf-2 Promotes the Generation of Colon Cancer Cells with Paneth Cell Properties to Drive Metastasis


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Mechanisms of Colon Cancer Metastasis Driven by Dickkopf-2 and Paneth Cell-like Cancer Cells