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Dickkopf-2 regulates the stem cell marker LGR5 in colorectal cancer via HNF4α1 : Dickkopf-2 regulates the stem cell marker LGR5 in colorectal cancer via HNF4 alpha 1

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dc.contributor.authorShin, Jae Hun-
dc.contributor.authorJeong, Jaekwang-
dc.contributor.authorChoi, Jungmin-
dc.contributor.authorLim, Jaechul-
dc.contributor.authorDinesh, Ravi K.-
dc.contributor.authorBraverman, Jonathan-
dc.contributor.authorHong, Jun Young-
dc.contributor.authorMaher, Stephen E.-
dc.contributor.authorAmezcua Vesely, Maria C.-
dc.contributor.authorKim, WonJu-
dc.contributor.authorKoo, Ja-Hyun-
dc.contributor.authorTang, Wenwen-
dc.contributor.authorWu, Dianqing-
dc.contributor.authorBlackburn, Holly N.-
dc.contributor.authorXicola, Rosa M.-
dc.contributor.authorLlor, Xavier-
dc.contributor.authorYilmaz, Omer-
dc.contributor.authorChoi, Je-Min-
dc.contributor.authorBothwell, Alfred L.M.-
dc.date.accessioned2024-05-08T01:57:11Z-
dc.date.available2024-05-08T01:57:11Z-
dc.date.created2023-05-03-
dc.date.created2023-05-03-
dc.date.created2023-05-03-
dc.date.created2023-05-03-
dc.date.created2023-05-03-
dc.date.issued2021-05-
dc.identifier.citationiScience, Vol.24 No.5, p. 102411-
dc.identifier.issn2589-0042-
dc.identifier.urihttps://hdl.handle.net/10371/201124-
dc.description.abstractEnhanced stemness in colorectal cancer has been reported and it contributes to aggressive progression, but the underlying mechanisms remain unclear. Here we report a Wnt ligand, Dickkopf-2 (DKK2) is essential for developing colorectal cancer stemness. Genetic depletion of DKK2 in intestinal epithelial or stem cells reduced tumorigenesis and expression of the stem cell marker genes including LGR5 in a model of colitis-associated cancer. Sequential mutations in APC, KRAS, TP53, and SMAD4 genes in colonic organoids revealed a significant increase of DKK2 expression by APC knockout and further increased by additional KRAS and TP53 mutations. Moreover, DKK2 activates proto-oncogene tyrosine-protein kinse Src followed by increased LGR5 expressing cells in colorectal cancer through degradation of HNF4 alpha 1 protein. These findings suggest that DKK2 is required for colonic epithelial cells to enhance LGR5 expression during the progression of colorectal cancer.-
dc.language영어-
dc.publisherCell Press-
dc.titleDickkopf-2 regulates the stem cell marker LGR5 in colorectal cancer via HNF4α1-
dc.title.alternativeDickkopf-2 regulates the stem cell marker LGR5 in colorectal cancer via HNF4 alpha 1-
dc.typeArticle-
dc.identifier.doi10.1016/j.isci.2021.102411-
dc.citation.journaltitleiScience-
dc.identifier.wosid000653990500026-
dc.identifier.scopusid2-s2.0-85104597591-
dc.citation.number5-
dc.citation.startpage102411-
dc.citation.volume24-
dc.description.isOpenAccessY-
dc.contributor.affiliatedAuthorLim, Jaechul-
dc.type.docTypeArticle-
dc.description.journalClass1-
dc.subject.keywordPlusINTESTINAL CRYPT-
dc.subject.keywordPlusSELF-RENEWAL-
dc.subject.keywordPlusCOLON-CANCER-
dc.subject.keywordPlusSRC-
dc.subject.keywordPlusTARGET-
dc.subject.keywordPlusGENE-
dc.subject.keywordPlusORIGIN-
dc.subject.keywordPlusFAMILY-
dc.subject.keywordPlusROLES-
dc.subject.keywordAuthorCancer-
dc.subject.keywordAuthorCell Biology-
dc.subject.keywordAuthorStem Cells Research-
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