Dickkopf-2 regulates the stem cell marker LGR5 in colorectal cancer via HNF4 alpha 1
DC Field | Value | Language |
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dc.contributor.author | Shin, Jae Hun | - |
dc.contributor.author | Jeong, Jaekwang | - |
dc.contributor.author | Choi, Jungmin | - |
dc.contributor.author | Lim, Jaechul | - |
dc.contributor.author | Dinesh, Ravi K. | - |
dc.contributor.author | Braverman, Jonathan | - |
dc.contributor.author | Hong, Jun Young | - |
dc.contributor.author | Maher, Stephen E. | - |
dc.contributor.author | Vesely, Maria C. Amezcua | - |
dc.contributor.author | Kim, WonJu | - |
dc.contributor.author | Koo, Ja-Hyun | - |
dc.contributor.author | Tang, Wenwen | - |
dc.contributor.author | Wu, Dianqing | - |
dc.contributor.author | Blackburn, Holly N. | - |
dc.contributor.author | Xicola, Rosa M. | - |
dc.contributor.author | Llor, Xavier | - |
dc.contributor.author | Yilmaz, Omer | - |
dc.contributor.author | Choi, Je-Min | - |
dc.contributor.author | Bothwell, Alfred L. M. | - |
dc.date.accessioned | 2021-11-19T16:40:33Z | - |
dc.date.available | 2021-11-19T16:40:33Z | - |
dc.date.created | 2021-08-30 | - |
dc.date.issued | 2021-05-21 | - |
dc.identifier.issn | 2589-0042 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/128013 | - |
dc.description.abstract | Enhanced 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.language | English | - |
dc.language.iso | en | - |
dc.publisher | CELL PRESS | - |
dc.subject | INTESTINAL CRYPT | - |
dc.subject | SELF-RENEWAL | - |
dc.subject | COLON-CANCER | - |
dc.subject | SRC | - |
dc.subject | TARGET | - |
dc.subject | GENE | - |
dc.subject | ORIGIN | - |
dc.subject | FAMILY | - |
dc.subject | ROLES | - |
dc.title | Dickkopf-2 regulates the stem cell marker LGR5 in colorectal cancer via HNF4 alpha 1 | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Choi, Jungmin | - |
dc.identifier.doi | 10.1016/j.isci.2021.102411 | - |
dc.identifier.scopusid | 2-s2.0-85104597591 | - |
dc.identifier.wosid | 000653990500026 | - |
dc.identifier.bibliographicCitation | ISCIENCE, v.24, no.5 | - |
dc.relation.isPartOf | ISCIENCE | - |
dc.citation.title | ISCIENCE | - |
dc.citation.volume | 24 | - |
dc.citation.number | 5 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.subject.keywordPlus | INTESTINAL CRYPT | - |
dc.subject.keywordPlus | SELF-RENEWAL | - |
dc.subject.keywordPlus | COLON-CANCER | - |
dc.subject.keywordPlus | SRC | - |
dc.subject.keywordPlus | TARGET | - |
dc.subject.keywordPlus | GENE | - |
dc.subject.keywordPlus | ORIGIN | - |
dc.subject.keywordPlus | FAMILY | - |
dc.subject.keywordPlus | ROLES | - |
dc.subject.keywordAuthor | Cancer | - |
dc.subject.keywordAuthor | Cell Biology | - |
dc.subject.keywordAuthor | Stem Cells Research | - |
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