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Article: Targeting cadherin-17 inactivates Wnt signaling and inhibits tumor growth in liver carcinoma

TitleTargeting cadherin-17 inactivates Wnt signaling and inhibits tumor growth in liver carcinoma
Authors
Issue Date2009
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/
Citation
Hepatology, 2009, v. 50 n. 5, p. 1453-1463 How to Cite?
Abstract
Hepatocellular carcinoma (HCC) is a lethal malignancy for which there are no effective therapies. To develop rational therapeutic approaches for treating this disease, we are performing proof-of-principle studies targeting molecules crucial for the development of HCC. Here, we show that cadherin-17 (CDH17) adhesion molecule is up-regulated in human liver cancers and can transform premalignant liver progenitor cells to produce liver carcinomas in mice. RNA interference-mediated knockdown of CDH17 inhibited proliferation of both primary and highly metastatic HCC cell lines in vitro and in vivo. The antitumor mechanisms underlying CDH17 inhibition involve inactivation of Wnt signaling, because growth inhibition and cell death were accompanied by relocalization of β-catenin to the cytoplasm and a concomitant reduction in cyclin D1 and an increase in retinoblastoma. Conclusion: Our results identify CDH17 as a novel oncogene in HCC and suggest that CDH17 is a biomarker and attractive therapeutic target for this aggressive malignancy. Copyright © 2009 by the American Association for the Study of Liver Diseases.
Persistent Identifierhttp://hdl.handle.net/10722/88591
ISSN
2013 Impact Factor: 11.190
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Research Grants Council of Hong KongHKU771607M
Collaborative Research FundHKU1/06C
National Cancer InstituteCA13106
Funding Information:

Supported by General Research Fund Grant HKU771607M from the Research Grants Council of Hong Kong (to J. M. L.). I. O. N. is Loke Yew Professor in Pathology and is supported by Collaborative Research Fund Grant HKU1/06C. S. W L. is a Howard Hughes Medical Institute investigator and is supported by National Cancer Institute Grant CA13106.

References

 

Author Affiliations
  1. Howard Hughes Medical Institute
  2. The University of Hong Kong
  3. Rosetta Inpharmatics LLC
  4. Fudan University
  5. Chinese University of Hong Kong
  6. Pfizer
DC FieldValueLanguage
dc.contributor.authorLiu, LXen_HK
dc.contributor.authorLee, NPen_HK
dc.contributor.authorChan, VWen_HK
dc.contributor.authorXue, Wen_HK
dc.contributor.authorZender, Len_HK
dc.contributor.authorZhang, Cen_HK
dc.contributor.authorMao, Men_HK
dc.contributor.authorDai, Hen_HK
dc.contributor.authorWang, XLen_HK
dc.contributor.authorXu, MZen_HK
dc.contributor.authorLee, TKen_HK
dc.contributor.authorNg, IOen_HK
dc.contributor.authorChen, Yen_HK
dc.contributor.authorKung, HFen_HK
dc.contributor.authorLowe, SWen_HK
dc.contributor.authorPoon, RTPen_HK
dc.contributor.authorWang, JHen_HK
dc.contributor.authorLuk, JMen_HK
dc.date.accessioned2010-09-06T09:45:23Z-
dc.date.available2010-09-06T09:45:23Z-
dc.date.issued2009en_HK
dc.identifier.citationHepatology, 2009, v. 50 n. 5, p. 1453-1463en_HK
dc.identifier.issn0270-9139en_HK
dc.identifier.urihttp://hdl.handle.net/10722/88591-
dc.description.abstractHepatocellular carcinoma (HCC) is a lethal malignancy for which there are no effective therapies. To develop rational therapeutic approaches for treating this disease, we are performing proof-of-principle studies targeting molecules crucial for the development of HCC. Here, we show that cadherin-17 (CDH17) adhesion molecule is up-regulated in human liver cancers and can transform premalignant liver progenitor cells to produce liver carcinomas in mice. RNA interference-mediated knockdown of CDH17 inhibited proliferation of both primary and highly metastatic HCC cell lines in vitro and in vivo. The antitumor mechanisms underlying CDH17 inhibition involve inactivation of Wnt signaling, because growth inhibition and cell death were accompanied by relocalization of β-catenin to the cytoplasm and a concomitant reduction in cyclin D1 and an increase in retinoblastoma. Conclusion: Our results identify CDH17 as a novel oncogene in HCC and suggest that CDH17 is a biomarker and attractive therapeutic target for this aggressive malignancy. Copyright © 2009 by the American Association for the Study of Liver Diseases.en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/en_HK
dc.relation.ispartofHepatologyen_HK
dc.rightsThe definitive version is available at www3.interscience.wiley.comen_HK
dc.subject.meshCadherins - genetics - metabolism-
dc.subject.meshCarcinoma, Hepatocellular - metabolism - pathology-
dc.subject.meshCell Proliferation-
dc.subject.meshLiver Neoplasms - metabolism - pathology-
dc.subject.meshSignal Transduction - physiology-
dc.titleTargeting cadherin-17 inactivates Wnt signaling and inhibits tumor growth in liver carcinomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0270-9139&volume=50&issue=5&spage=1453&epage=1463&date=2009&atitle=Targeting+cadherin-17+inactivates+Wnt+signaling+and+inhibits+tumor+growth+in+liver+carcinomaen_HK
dc.identifier.emailLee, NP: nikkilee@hku.hken_HK
dc.identifier.emailLee, TK: tkwlee@hkucc.hku.hken_HK
dc.identifier.emailNg, IO: iolng@hkucc.hku.hken_HK
dc.identifier.emailPoon, RTP: poontp@hkucc.hku.hken_HK
dc.identifier.emailLuk, JM: jmluk@hkucc.hku.hken_HK
dc.identifier.authorityLee, NP=rp00263en_HK
dc.identifier.authorityLee, TK=rp00447en_HK
dc.identifier.authorityNg, IO=rp00335en_HK
dc.identifier.authorityPoon, RTP=rp00446en_HK
dc.identifier.authorityLuk, JM=rp00349en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/hep.23143en_HK
dc.identifier.pmid19676131en_HK
dc.identifier.pmcidPMC3328302-
dc.identifier.scopuseid_2-s2.0-72949084408en_HK
dc.identifier.hkuros168580en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-72949084408&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume50en_HK
dc.identifier.issue5en_HK
dc.identifier.spage1453en_HK
dc.identifier.epage1463en_HK
dc.identifier.eissn1527-3350-
dc.identifier.isiWOS:000271565600017-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLiu, LX=13611939300en_HK
dc.identifier.scopusauthoridLee, NP=7402722690en_HK
dc.identifier.scopusauthoridChan, VW=36005663800en_HK
dc.identifier.scopusauthoridXue, W=32267773000en_HK
dc.identifier.scopusauthoridZender, L=6603035987en_HK
dc.identifier.scopusauthoridZhang, C=7405492903en_HK
dc.identifier.scopusauthoridMao, M=7102960472en_HK
dc.identifier.scopusauthoridDai, H=7402206916en_HK
dc.identifier.scopusauthoridWang, XL=9733112300en_HK
dc.identifier.scopusauthoridXu, MZ=24339881700en_HK
dc.identifier.scopusauthoridLee, TK=7501439435en_HK
dc.identifier.scopusauthoridNg, IO=7102753722en_HK
dc.identifier.scopusauthoridChen, Y=24075600300en_HK
dc.identifier.scopusauthoridKung, HF=7402514190en_HK
dc.identifier.scopusauthoridLowe, SW=15064198100en_HK
dc.identifier.scopusauthoridPoon, RTP=7103097223en_HK
dc.identifier.scopusauthoridWang, JH=8898010700en_HK
dc.identifier.scopusauthoridLuk, JM=7006777791en_HK

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