Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0072386
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dc.titleAnti-cadherin-17 antibody modulates beta-catenin signaling and tumorigenicity of hepatocellular carcinoma
dc.contributor.authorWang Y.
dc.contributor.authorShek F.H.
dc.contributor.authorWong K.F.
dc.contributor.authorLiu L.X.
dc.contributor.authorZhang X.Q.
dc.contributor.authorYuan Y.
dc.contributor.authorKhin E.
dc.contributor.authorHu M.-Y.
dc.contributor.authorWang J.H.
dc.contributor.authorPoon R.T.P.
dc.contributor.authorHong W.
dc.contributor.authorLee N.P.
dc.contributor.authorLuk J.M.
dc.date.accessioned2019-11-05T02:13:04Z
dc.date.available2019-11-05T02:13:04Z
dc.date.issued2013
dc.identifier.citationWang Y., Shek F.H., Wong K.F., Liu L.X., Zhang X.Q., Yuan Y., Khin E., Hu M.-Y., Wang J.H., Poon R.T.P., Hong W., Lee N.P., Luk J.M. (2013). Anti-cadherin-17 antibody modulates beta-catenin signaling and tumorigenicity of hepatocellular carcinoma. PLoS ONE 8 (9) : e72386. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0072386
dc.identifier.issn1932-6203
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/161467
dc.description.abstractCadherin-17 (CDH17) is an oncofetal molecule associated with poor prognostic outcomes of hepatocellular carcinoma (HCC), for which the treatment options are very limited. The present study investigates the therapeutic potential of a monoclonal antibody (Lic5) that targets the CDH17 antigen in HCC. In vitro experiments showed Lic5 could markedly reduce CDH17 expression in a dose-dependent manner, suppress b-catenin signaling, and induce cleavages of apoptotic enzymes caspase-8 and -9 in HCC cells. Treatment of animals in subcutaneous HCC xenograft model similarly demonstrated significant tumor growth inhibition (TGI) using Lic5 antibody alone (5 mg/kg, i.p., t.i.w.; ca.60-65% TGI vs. vehicle at day 28), or in combination with conventional chemotherapy regimen (cisplatin 1 mg/kg; ca. 85-90% TGI). Strikingly, lung metastasis was markedly suppressed by Lic5 treatments. Immunohistochemical and western blot analyses of xenograft explants revealed inactivation of the Wnt pathway and suppression of Wnt signaling components in HCC tissues. Collectively, anti-CDH17 antibody promises as an effective biologic agent for treating malignant HCC. © 2013 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20191101
dc.subjectantineoplastic agent
dc.subjectbeta catenin
dc.subjectcadherin
dc.subjectcadherin 17
dc.subjectcadherin 17 antibody
dc.subjectcaspase 8
dc.subjectcaspase 9
dc.subjectcisplatin
dc.subjectLic5 antibody
dc.subjectmonoclonal antibody
dc.subjectprotein antibody
dc.subjectunclassified drug
dc.subjectWnt protein
dc.subjectantineoplastic agent
dc.subjectbeta catenin
dc.subjectcadherin
dc.subjectCASP8 protein, human
dc.subjectCASP9 protein, human
dc.subjectcaspase 8
dc.subjectcaspase 9
dc.subjectCDH17 protein, human
dc.subjectCTNNB1 protein, human
dc.subjectmonoclonal antibody
dc.subjectanimal cell
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectantigen expression
dc.subjectapoptosis
dc.subjectArticle
dc.subjectbeta catenin signaling
dc.subjectcancer combination chemotherapy
dc.subjectcancer inhibition
dc.subjectcancer model
dc.subjectcancer tissue
dc.subjectcarcinogenicity
dc.subjectcarcinoma cell
dc.subjectconcentration response
dc.subjectcontrolled study
dc.subjectdrug targeting
dc.subjecthuman
dc.subjecthuman cell
dc.subjectimmunohistochemistry
dc.subjectin vitro study
dc.subjectliver cell carcinoma
dc.subjectlung metastasis
dc.subjectmouse
dc.subjectnonhuman
dc.subjectprotein cleavage
dc.subjectrandomized controlled trial
dc.subjectsubcutaneous tissue tumor
dc.subjectsynaptic transmission
dc.subjecttumor xenograft
dc.subjectWestern blotting
dc.subjectWnt signaling
dc.subjectanimal
dc.subjectarticle
dc.subjectBagg albino mouse
dc.subjectcarcinogenesis
dc.subjectdrug effect
dc.subjectdrug screening
dc.subjectimmunology
dc.subjectliver tumor
dc.subjectmetabolism
dc.subjecttumor cell line
dc.subjecttumor volume
dc.subjectWnt signaling pathway
dc.subjectAnimals
dc.subjectAntibodies, Monoclonal
dc.subjectAntineoplastic Agents
dc.subjectbeta Catenin
dc.subjectCadherins
dc.subjectCarcinogenesis
dc.subjectCarcinoma, Hepatocellular
dc.subjectCaspase 8
dc.subjectCaspase 9
dc.subjectCell Line, Tumor
dc.subjectHumans
dc.subjectLiver Neoplasms
dc.subjectMice
dc.subjectMice, Inbred BALB C
dc.subjectTumor Burden
dc.subjectWnt Signaling Pathway
dc.subjectXenograft Model Antitumor Assays
dc.typeArticle
dc.contributor.departmentDEPT OF BIOCHEMISTRY
dc.contributor.departmentINSTITUTE OF MOLECULAR & CELL BIOLOGY
dc.description.doi10.1371/journal.pone.0072386
dc.description.sourcetitlePLoS ONE
dc.description.volume8
dc.description.issue9
dc.description.pagee72386
dc.published.statePublished
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This item is licensed under a Creative Commons License Creative Commons