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Article: Prickle-1 Negatively Regulates Wnt/β-Catenin Pathway by Promoting Dishevelled Ubiquitination/Degradation in Liver Cancer

TitlePrickle-1 Negatively Regulates Wnt/β-Catenin Pathway by Promoting Dishevelled Ubiquitination/Degradation in Liver Cancer
Authors
Issue Date2006
PublisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/gastro
Citation
Gastroenterology, 2006, v. 131 n. 4, p. 1218-1227 How to Cite?
AbstractBackground & Aims: Aberrant activation of Wnt signaling due to accumulation of β-catenin has been linked to tumorigenesis. Mutations of β-catenin, APC, and axins are important but not frequent enough to be accountable for the accumulation of β-catenin in human hepatocellular carcinoma (HCC). In this study, we characterized the roles of Prickle-1, a Dishevelled (Dvl)-associated protein, in regulation of Wnt/β-catenin activity in HCC. Methods: The expression levels of human Prickle-1 and Dvl3 were examined in HCC cell lines and human HCC samples. The interaction and effects of Prickle-1 on Dvl3, the Wnt/β-catenin pathway, and cell growth were assessed in HCC cell lines. Results: We showed that Prickle-1 bound with Dvl3 and facilitated Dvl3 ubiquitination/degradation, and this was through its destruction box (D-box) motifs. Enforced expression of Prickle-1 significantly reduced the Wnt/β-catenin activity and tumorigenic properties of HCC cells. Clinicopathologic analysis showed that underexpression of Prickle-1 was significantly associated with overexpression of Dvl3, β-catenin accumulation (P = .023), and larger tumor size (P = .030). Conclusions: Our results have elucidated a novel mechanistic relationship between Prickle-1 and Dvl3 in the Wnt/β-catenin pathway. The facilitation of Prickle-1 on Dvl3 degradation and the suppression of β-catenin activity and cell growth suggest that Prickle-1 is a negative regulator of the Wnt/β-catenin signaling pathway and is a putative tumor suppressor in human HCCs. © 2006 American Gastroenterological Association (AGA) Institute.
Persistent Identifierhttp://hdl.handle.net/10722/148482
ISSN
2015 Impact Factor: 18.187
2015 SCImago Journal Rankings: 7.170
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChan, DWen_HK
dc.contributor.authorChan, Cen_HK
dc.contributor.authorYam, JWPen_HK
dc.contributor.authorChing, Yen_HK
dc.contributor.authorNg, IOLen_HK
dc.date.accessioned2012-05-29T06:13:13Z-
dc.date.available2012-05-29T06:13:13Z-
dc.date.issued2006en_HK
dc.identifier.citationGastroenterology, 2006, v. 131 n. 4, p. 1218-1227en_HK
dc.identifier.issn0016-5085en_HK
dc.identifier.urihttp://hdl.handle.net/10722/148482-
dc.description.abstractBackground & Aims: Aberrant activation of Wnt signaling due to accumulation of β-catenin has been linked to tumorigenesis. Mutations of β-catenin, APC, and axins are important but not frequent enough to be accountable for the accumulation of β-catenin in human hepatocellular carcinoma (HCC). In this study, we characterized the roles of Prickle-1, a Dishevelled (Dvl)-associated protein, in regulation of Wnt/β-catenin activity in HCC. Methods: The expression levels of human Prickle-1 and Dvl3 were examined in HCC cell lines and human HCC samples. The interaction and effects of Prickle-1 on Dvl3, the Wnt/β-catenin pathway, and cell growth were assessed in HCC cell lines. Results: We showed that Prickle-1 bound with Dvl3 and facilitated Dvl3 ubiquitination/degradation, and this was through its destruction box (D-box) motifs. Enforced expression of Prickle-1 significantly reduced the Wnt/β-catenin activity and tumorigenic properties of HCC cells. Clinicopathologic analysis showed that underexpression of Prickle-1 was significantly associated with overexpression of Dvl3, β-catenin accumulation (P = .023), and larger tumor size (P = .030). Conclusions: Our results have elucidated a novel mechanistic relationship between Prickle-1 and Dvl3 in the Wnt/β-catenin pathway. The facilitation of Prickle-1 on Dvl3 degradation and the suppression of β-catenin activity and cell growth suggest that Prickle-1 is a negative regulator of the Wnt/β-catenin signaling pathway and is a putative tumor suppressor in human HCCs. © 2006 American Gastroenterological Association (AGA) Institute.en_HK
dc.languageengen_US
dc.publisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/gastroen_HK
dc.relation.ispartofGastroenterologyen_HK
dc.subject.meshAdaptor Proteins, Signal Transducing - Genetics - Metabolismen_US
dc.subject.meshAmino Acid Sequenceen_US
dc.subject.meshCarcinoma, Hepatocellular - Metabolism - Pathology - Physiopathologyen_US
dc.subject.meshCell Division - Physiologyen_US
dc.subject.meshCell Lineen_US
dc.subject.meshConsensus Sequenceen_US
dc.subject.meshGene Expression Regulation, Neoplasticen_US
dc.subject.meshHumansen_US
dc.subject.meshKidney - Cytologyen_US
dc.subject.meshLim Domain Proteinsen_US
dc.subject.meshLiver Neoplasms - Metabolism - Pathology - Physiopathologyen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshPhosphoproteins - Genetics - Metabolismen_US
dc.subject.meshSignal Transduction - Physiologyen_US
dc.subject.meshTumor Suppressor Proteins - Genetics - Metabolismen_US
dc.subject.meshUbiquitin - Metabolismen_US
dc.subject.meshWnt Proteins - Metabolismen_US
dc.subject.meshBeta Catenin - Metabolismen_US
dc.titlePrickle-1 Negatively Regulates Wnt/β-Catenin Pathway by Promoting Dishevelled Ubiquitination/Degradation in Liver Canceren_HK
dc.typeArticleen_HK
dc.identifier.emailChan, DW:dwchan@hkucc.hku.hken_HK
dc.identifier.emailYam, JWP:judyyam@pathology.hku.hken_HK
dc.identifier.emailChing, Y:ypching@hku.hken_HK
dc.identifier.emailNg, IOL:iolng@hkucc.hku.hken_HK
dc.identifier.authorityChan, DW=rp00543en_HK
dc.identifier.authorityYam, JWP=rp00468en_HK
dc.identifier.authorityChing, Y=rp00469en_HK
dc.identifier.authorityNg, IOL=rp00335en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1053/j.gastro.2006.07.020en_HK
dc.identifier.pmid17030191-
dc.identifier.scopuseid_2-s2.0-33749501476en_HK
dc.identifier.hkuros124306-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33749501476&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume131en_HK
dc.identifier.issue4en_HK
dc.identifier.spage1218en_HK
dc.identifier.epage1227en_HK
dc.identifier.eissn1528-0012-
dc.identifier.isiWOS:000241246800031-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridChan, DW=26533900600en_HK
dc.identifier.scopusauthoridChan, C=8277448300en_HK
dc.identifier.scopusauthoridYam, JWP=6603711123en_HK
dc.identifier.scopusauthoridChing, Y=7005431277en_HK
dc.identifier.scopusauthoridNg, IOL=7102753722en_HK

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