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Niclosamide is a potential therapeutic for familial adenomatosis polyposis by disrupting Axin-GSK3 interaction

DC FieldValueLanguage
dc.contributor.author김현실-
dc.contributor.author차소영-
dc.contributor.author차용훈-
dc.contributor.author안성용-
dc.contributor.author김남희-
dc.contributor.author양지혜-
dc.contributor.author육종인-
dc.contributor.author조은애-
dc.date.accessioned2017-11-01T08:56:37Z-
dc.date.available2017-11-01T08:56:37Z-
dc.date.issued2017-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/153827-
dc.description.abstractThe epithelial-mesenchymal transition (EMT) is implicated in tumorigenesis and cancer progression, and canonical Wnt signaling tightly controls Snail, a key transcriptional repressor of EMT. While the suppression of canonical Wnt signaling and EMT comprises an attractive therapeutic strategy, molecular targets for small molecules reverting Wnt and EMT have not been widely studied. Meanwhile, the anti-helminthic niclosamide has been identified as a potent inhibitor of many oncogenic signaling pathways although its molecular targets have not yet been clearly identified. In this study, we show that niclosamide directly targets Axin-GSK3 interaction, at least in part, resulting in suppression of Wnt/Snail-mediated EMT. In vitro and in vivo, disruption of Axin-GSK3 complex by niclosamide induces mesenchymal to epithelial reversion at nM concentrations, accompanied with suppression of the tumorigenic potential of colon cancer. Niclosamide treatment successfully attenuates Snail abundance while increasing E-cadherin abundance in xenograft tumor. Notably, oral administration of niclosamide significantly suppressed adenoma formation in an APC-MIN mice model, indicating that niclosamide is an effective therapeutic for familial adenomatosis polyposis (FAP) patients. In this study, we identified a novel target to control the canonical Wnt pathway and Snail-mediated EMT program, and discovered a repositioned therapeutics for FAP patients.-
dc.description.statementOfResponsibilityopen-
dc.formatapplication/pdf-
dc.languageEnglish-
dc.publisherImpact Journals-
dc.relation.isPartOfOncotarget-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAdenomatous Polyposis Coli/drug therapy-
dc.subject.MESHAdenomatous Polyposis Coli/genetics-
dc.subject.MESHAdenomatous Polyposis Coli/metabolism*-
dc.subject.MESHAnimals-
dc.subject.MESHAxin Protein/chemistry-
dc.subject.MESHAxin Protein/metabolism*-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHCell Movement/drug effects-
dc.subject.MESHCell Survival/drug effects-
dc.subject.MESHDisease Models, Animal-
dc.subject.MESHEpithelial-Mesenchymal Transition/drug effects-
dc.subject.MESHGlycogen Synthase Kinase 3/chemistry-
dc.subject.MESHGlycogen Synthase Kinase 3/metabolism*-
dc.subject.MESHHeterografts-
dc.subject.MESHMice-
dc.subject.MESHModels, Molecular-
dc.subject.MESHMolecular Conformation-
dc.subject.MESHNiclosamide/chemistry-
dc.subject.MESHNiclosamide/pharmacology*-
dc.subject.MESHProtein Binding/drug effects-
dc.subject.MESHWnt Signaling Pathway/drug effects-
dc.titleNiclosamide is a potential therapeutic for familial adenomatosis polyposis by disrupting Axin-GSK3 interaction-
dc.typeArticle-
dc.publisher.locationUnited States-
dc.contributor.collegeCollege of Dentistry-
dc.contributor.departmentDept. of Oral Pathology-
dc.contributor.googleauthorSung Yong Ahn-
dc.contributor.googleauthorNam Hee Kim-
dc.contributor.googleauthorKyungro Lee-
dc.contributor.googleauthorYong Hoon Cha-
dc.contributor.googleauthorJi Hye Yang-
dc.contributor.googleauthorSo Young Cha-
dc.contributor.googleauthorEunae Sandra Cho-
dc.contributor.googleauthorYoonmi Lee-
dc.contributor.googleauthorJeong Seok Cha-
dc.contributor.googleauthorHyun Soo Cho-
dc.contributor.googleauthorYoon Jeon-
dc.contributor.googleauthorYoung-Su Yuk-
dc.contributor.googleauthorSuebean Cho-
dc.contributor.googleauthorKyoung Tai No-
dc.contributor.googleauthorHyun Sil Kim-
dc.contributor.googleauthorHo Lee-
dc.contributor.googleauthorJiwon Choi-
dc.contributor.googleauthorJong In Yook-
dc.identifier.doi10.18632/oncotarget.16252-
dc.contributor.localIdA03997-
dc.contributor.localIdA04000-
dc.contributor.localIdA05145-
dc.contributor.localIdA00360-
dc.contributor.localIdA05149-
dc.contributor.localIdA02536-
dc.contributor.localIdA01121-
dc.relation.journalcodeJ02421-
dc.identifier.eissn1949-2553-
dc.identifier.pmid28418862-
dc.subject.keywordAxin-GSK3 interaction-
dc.subject.keywordWnt signaling-
dc.subject.keywordepithelial-mesenchymal transition (EMT)-
dc.subject.keywordfamilial adenomatosis polyposis (FAP)-
dc.subject.keywordniclosamide-
dc.contributor.alternativeNameKim, Hyun Sil-
dc.contributor.alternativeNameCha, So Young-
dc.contributor.alternativeNameCha, Yong Hoon-
dc.contributor.alternativeNameAhn, Sung Yong-
dc.contributor.alternativeNameKim, Nam Hee-
dc.contributor.alternativeNameYang, Ji Hye-
dc.contributor.alternativeNameYook, Jong In-
dc.contributor.affiliatedAuthorCha, So Young-
dc.contributor.affiliatedAuthorCha, Yong Hoon-
dc.contributor.affiliatedAuthorAhn, Sung Yong-
dc.contributor.affiliatedAuthorKim, Nam Hee-
dc.contributor.affiliatedAuthorYang, Ji Hye-
dc.contributor.affiliatedAuthorYook, Jong In-
dc.contributor.affiliatedAuthorKim, Hyun Sil-
dc.citation.titleOncotarget-
dc.citation.volume8-
dc.citation.number19-
dc.citation.startPage31842-
dc.citation.endPage31855-
dc.identifier.bibliographicCitationOncotarget, Vol.8(19) : 31842-31855, 2017-
dc.date.modified2017-11-01-
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral and Maxillofacial Surgery (구강악안면외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Oral Cancer Research Institute (구강종양연구소) > 1. Journal Papers

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