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Metformin and Niclosamide Synergistically Suppress Wnt and YAP in APC-Mutated Colorectal Cancer

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dc.contributor.author김남희-
dc.contributor.author김태일-
dc.contributor.author김현실-
dc.contributor.author육종인-
dc.contributor.author조은애산드라-
dc.contributor.author김태일-
dc.contributor.author김현실-
dc.contributor.author육종인-
dc.contributor.author조은애산드라-
dc.date.accessioned2021-09-29T01:18:16Z-
dc.date.available2021-09-29T01:18:16Z-
dc.date.issued2021-07-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/184298-
dc.description.abstractThe Wnt and Hippo pathways are tightly coordinated and understanding their reciprocal regulation may provide a novel therapeutic strategy for cancer. Anti-helminthic niclosamide is an effective inhibitor of Wnt and is now in a phase II trial for advanced colorectal cancer (CRC) patients. We found that Axin2, an authentic target gene of canonical Wnt, acts as aYAP phosphorylation activator in APC-mutated CRC. While niclosamide effectively suppresses Wnt, it also inhibits Hippo, limiting its therapeutic potential for CRC. To overcome this limitation, we utilized metformin, a clinically available AMPK activator. This combinatory approach not only suppresses canonical Wnt activity, but also inhibits YAP activity in CRC cancer cells and in patient-derived cancer organoid through the suppression of cancer stemness. Further, combinatory oral administration suppressed in vivo tumorigenesis and the cancer progression of APC-MIN mice models. Our observations provide not only a reciprocal link between Wnt and Hippo, but also clinically available novel therapeutics that are able to target Wnt and YAP in APC-mutated CRC.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherMDPI-
dc.relation.isPartOfCANCERS-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.titleMetformin and Niclosamide Synergistically Suppress Wnt and YAP in APC-Mutated Colorectal Cancer-
dc.typeArticle-
dc.contributor.collegeCollege of Dentistry (치과대학)-
dc.contributor.departmentResearch Institute (부설연구소)-
dc.contributor.googleauthorHee Eun Kang-
dc.contributor.googleauthorYoojeong Seo-
dc.contributor.googleauthorJun Seop Yun-
dc.contributor.googleauthorSang Hyun Song-
dc.contributor.googleauthorDawool Han-
dc.contributor.googleauthorEunae Sandra Cho-
dc.contributor.googleauthorSue Bean Cho-
dc.contributor.googleauthorYoon Jeon-
dc.contributor.googleauthorHo Lee Hyun Sil Kim-
dc.contributor.googleauthorJoyeon Kang-
dc.contributor.googleauthorJong In Yook-
dc.contributor.googleauthorNam Hee Kim-
dc.contributor.googleauthorTae Il Kim-
dc.identifier.doi10.3390/cancers13143437-
dc.contributor.localIdA00360-
dc.contributor.localIdA01079-
dc.contributor.localIdA01121-
dc.contributor.localIdA02536-
dc.contributor.localIdA04799-
dc.contributor.localIdA01079-
dc.contributor.localIdA01121-
dc.contributor.localIdA02536-
dc.contributor.localIdA04799-
dc.relation.journalcodeJ03449-
dc.identifier.eissn2072-6694-
dc.identifier.pmid34298652-
dc.subject.keywordHippo-
dc.subject.keywordWnt-
dc.subject.keywordcolorectal cancer-
dc.subject.keywordmetformin-
dc.subject.keywordniclosamide-
dc.contributor.alternativeNameKim, Nam Hee-
dc.contributor.affiliatedAuthor김남희-
dc.contributor.affiliatedAuthor김태일-
dc.contributor.affiliatedAuthor김현실-
dc.contributor.affiliatedAuthor육종인-
dc.contributor.affiliatedAuthor조은애산드라-
dc.contributor.affiliatedAuthor김태일-
dc.contributor.affiliatedAuthor김현실-
dc.contributor.affiliatedAuthor육종인-
dc.contributor.affiliatedAuthor조은애산드라-
dc.citation.volume13-
dc.citation.number14-
dc.citation.startPage3437-
dc.identifier.bibliographicCitationCANCERS, Vol.13(14) : 3437, 2021-07-
Appears in Collections:
2. College of Dentistry (치과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers

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