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Article: The human cadherin 11 is a pro-apoptotic tumor suppressor modulating cell stemness through Wnt/β-catenin signaling and silenced in common carcinomas

TitleThe human cadherin 11 is a pro-apoptotic tumor suppressor modulating cell stemness through Wnt/β-catenin signaling and silenced in common carcinomas
Authors
Issue Date2012
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2012, v. 31 n. 34, p. 3901-3912 How to Cite?
Abstract
Genetic alterations of 16q21-q22, the locus of a 6-cadherin cluster, are frequently involved in multiple tumors, suggesting the presence of critical tumor suppressor genes (TSGs). Using 1 Mb array comparative genomic hybridization (aCGH), we refined a small hemizygous deletion (1 Mb) at 16q21-22.1, which contains a single gene Cadherin-11 (CDH11, OB-cadherin). CDH11 was broadly expressed in human normal adult and fetal tissues, while its silencing and promoter CpG methylation were frequently detected in tumor cell lines, but not in immortalized normal epithelial cells. Aberrant methylation was also frequently detected in multiple primary tumors. CDH11 silencing could be reversed by pharmacologic or genetic demethylation, indicating an epigenetic mechanism. Ectopic expression of CDH11 strongly suppressed tumorigenecity and induced tumor cell apoptosis. Moreover, CDH11 was found to inhibit Wnt/beta-catenin and AKT/Rho A signaling, as well as actin stress fiber formation, thus further inhibiting tumor cell migration and invasion. CDH11 also inhibited epithelial-to-mesenchymal transition and downregulated stem cell markers. Thus, our work identifies CDH11 as a functional tumor suppressor and an important antagonist of Wnt/beta-catenin and AKT/Rho A signaling, with frequent epigenetic inactivation in common carcinomas.
Persistent Identifierhttp://hdl.handle.net/10722/148663
ISSN
2013 Impact Factor: 8.559
2013 SCImago Journal Rankings: 4.764
PubMed Central ID
ISI Accession Number ID

 

Author Affiliations
  1. The University of Hong Kong
  2. Johns Hopkins Singapore
  3. Beijing Cancer Hospital
  4. Central South University China
  5. Chinese University of Hong Kong
DC FieldValueLanguage
dc.contributor.authorLi, Len_US
dc.contributor.authorYing, Jen_US
dc.contributor.authorLi, Hen_US
dc.contributor.authorZhang, Yen_US
dc.contributor.authorShu, Xen_US
dc.contributor.authorFan, Yen_US
dc.contributor.authorTan, Jen_US
dc.contributor.authorCao, Yen_US
dc.contributor.authorTsao, SWen_US
dc.contributor.authorSrivastava, Gen_US
dc.contributor.authorChan, ATCen_US
dc.contributor.authorTao, Qen_US
dc.date.accessioned2012-05-29T06:14:31Z-
dc.date.available2012-05-29T06:14:31Z-
dc.date.issued2012en_US
dc.identifier.citationOncogene, 2012, v. 31 n. 34, p. 3901-3912en_US
dc.identifier.issn0950-9232en_US
dc.identifier.urihttp://hdl.handle.net/10722/148663-
dc.description.abstractGenetic alterations of 16q21-q22, the locus of a 6-cadherin cluster, are frequently involved in multiple tumors, suggesting the presence of critical tumor suppressor genes (TSGs). Using 1 Mb array comparative genomic hybridization (aCGH), we refined a small hemizygous deletion (1 Mb) at 16q21-22.1, which contains a single gene Cadherin-11 (CDH11, OB-cadherin). CDH11 was broadly expressed in human normal adult and fetal tissues, while its silencing and promoter CpG methylation were frequently detected in tumor cell lines, but not in immortalized normal epithelial cells. Aberrant methylation was also frequently detected in multiple primary tumors. CDH11 silencing could be reversed by pharmacologic or genetic demethylation, indicating an epigenetic mechanism. Ectopic expression of CDH11 strongly suppressed tumorigenecity and induced tumor cell apoptosis. Moreover, CDH11 was found to inhibit Wnt/beta-catenin and AKT/Rho A signaling, as well as actin stress fiber formation, thus further inhibiting tumor cell migration and invasion. CDH11 also inhibited epithelial-to-mesenchymal transition and downregulated stem cell markers. Thus, our work identifies CDH11 as a functional tumor suppressor and an important antagonist of Wnt/beta-catenin and AKT/Rho A signaling, with frequent epigenetic inactivation in common carcinomas.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/oncen_US
dc.relation.ispartofOncogeneen_US
dc.subject.meshCadherins - genetics - metabolism-
dc.subject.meshSignal Transduction-
dc.subject.meshTumor Suppressor Proteins - genetics - metabolism-
dc.subject.meshWnt Proteins - metabolism-
dc.subject.meshbeta Catenin - metabolism-
dc.titleThe human cadherin 11 is a pro-apoptotic tumor suppressor modulating cell stemness through Wnt/β-catenin signaling and silenced in common carcinomasen_US
dc.typeArticleen_US
dc.identifier.emailTsao, SW: gswtsao@hku.hken_US
dc.identifier.emailSrivastava, G: sgopesh@hkucc.hku.hk-
dc.identifier.emailTao, Q: qtao@clo.cuhk.edu.hk-
dc.identifier.authoritySrivastava, G=rp00365en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1038/onc.2011.541en_US
dc.identifier.pmid22139084-
dc.identifier.pmcidPMC3426851-
dc.identifier.scopuseid_2-s2.0-84865417923en_US
dc.identifier.hkuros207508-
dc.identifier.hkuros217742-
dc.identifier.volume31-
dc.identifier.issue34-
dc.identifier.spage3901-
dc.identifier.epage3912-
dc.identifier.isiWOS:000307925000007-
dc.publisher.placeUnited Kingdomen_US

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