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Article: Upregulation of the Wnt co-receptor LRP6 promotes hepatocarcinogenesis and enhances cell invasion

TitleUpregulation of the Wnt co-receptor LRP6 promotes hepatocarcinogenesis and enhances cell invasion
Authors
KeywordsAnimal cell
Carcinogenicity
Carcinoma cell
Cell invasion
Cell migration
Issue Date2012
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
PLoS One, 2012, v. 7 n. 5, article no. e36565 How to Cite?
AbstractBACKGROUND: Activation of the Wnt/beta-catenin signaling pathway plays a crucial role in hepatocellular carcinoma (HCC). Low-density lipoprotein (LDL) receptor-related protein-6 (LRP6) is one of the co-receptors of the Wnt/beta-catenin pathway and forms a signaling complex with Wnt ligand and Frizzled receptor to activate downstream signaling. However, the role of LRP6 in hepatocarcinogenesis is unclear. In this study, we examined its expression and roles in human HCC. METHODOLOGY/PRINCIPAL FINDINGS: Using real-time quantitative RT-PCR, we found that LRP6 was frequently (45%) overexpressed in human HCCs (P = 0.003). In vitro studies showed that ectopic expression of LRP6 increased the protein level of beta-catenin. Moreover, overexpression of the full-length and constitutively active LRP6, respectively, activated the WNT/beta-catenin signaling pathway, as shown by the TCF/beta-catenin reporter assay. With regard to the effects of LRP6 overexpression in HCC cells, stable overexpression of the constitutively active LRP6 in BEL-7402 HCC cells enhanced cell proliferation, cell migration, and invasion in vitro as well as tumorigenicity in nude mice. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that overexpression of LRP6 contributes to the hyperactivation of the Wnt/beta-catenin signaling pathway in human HCCs and suggest it may play a role in hepatocarcinogenesis.
Persistent Identifierhttp://hdl.handle.net/10722/160060
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorTung, EKKen_US
dc.contributor.authorWong, BYCen_US
dc.contributor.authorYau, TOen_US
dc.contributor.authorNg, IOLen_US
dc.date.accessioned2012-08-16T06:02:10Z-
dc.date.available2012-08-16T06:02:10Z-
dc.date.issued2012en_US
dc.identifier.citationPLoS One, 2012, v. 7 n. 5, article no. e36565en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://hdl.handle.net/10722/160060-
dc.description.abstractBACKGROUND: Activation of the Wnt/beta-catenin signaling pathway plays a crucial role in hepatocellular carcinoma (HCC). Low-density lipoprotein (LDL) receptor-related protein-6 (LRP6) is one of the co-receptors of the Wnt/beta-catenin pathway and forms a signaling complex with Wnt ligand and Frizzled receptor to activate downstream signaling. However, the role of LRP6 in hepatocarcinogenesis is unclear. In this study, we examined its expression and roles in human HCC. METHODOLOGY/PRINCIPAL FINDINGS: Using real-time quantitative RT-PCR, we found that LRP6 was frequently (45%) overexpressed in human HCCs (P = 0.003). In vitro studies showed that ectopic expression of LRP6 increased the protein level of beta-catenin. Moreover, overexpression of the full-length and constitutively active LRP6, respectively, activated the WNT/beta-catenin signaling pathway, as shown by the TCF/beta-catenin reporter assay. With regard to the effects of LRP6 overexpression in HCC cells, stable overexpression of the constitutively active LRP6 in BEL-7402 HCC cells enhanced cell proliferation, cell migration, and invasion in vitro as well as tumorigenicity in nude mice. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that overexpression of LRP6 contributes to the hyperactivation of the Wnt/beta-catenin signaling pathway in human HCCs and suggest it may play a role in hepatocarcinogenesis.-
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action-
dc.relation.ispartofPLoS Oneen_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectAnimal cell-
dc.subjectCarcinogenicity-
dc.subjectCarcinoma cell-
dc.subjectCell invasion-
dc.subjectCell migration-
dc.titleUpregulation of the Wnt co-receptor LRP6 promotes hepatocarcinogenesis and enhances cell invasionen_US
dc.typeArticleen_US
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1932-6203 (Electronic) 1932-6203 (Linkin&volume=7&issue=5&spage=e36565&epage=&date=2012&atitle=Upregulation+of+the+Wnt+co-receptor+LRP6+promotes+hepatocarcinogenesis+and+enhances+cell+invasionen_US
dc.identifier.emailTung, EKK: edmund@pathology.hku.hken_US
dc.identifier.emailYau, TO: yauto@hkucc.hku.hken_US
dc.identifier.emailNg, IOL: iolng@hku.hken_US
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0036565-
dc.identifier.pmid22570728-
dc.identifier.pmcidPMC3343020-
dc.identifier.scopuseid_2-s2.0-84860524549-
dc.identifier.hkuros204789en_US
dc.identifier.volume7en_US
dc.identifier.issue5, article no. e36565en_US
dc.publisher.placeUnited States-

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