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

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TitleThe human cadherin 11 is a pro-apoptotic tumor suppressor modulating cell stemness through Wnt/β-catenin signaling and silenced in common carcinomas
AuthorsLi, L5
Ying, J2 5
Li, H5
Zhang, Y5
Shu, X5
Fan, Y5
Tan, J3
Cao, Y4
Tsao, SW1
Srivastava, G1
Chan, ATC5
Tao, Q5
Issue Date2011
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
CitationOncogene, 2011, v. 31 n. 34, p. 3901-3912 [How to Cite?]
DOI: http://dx.doi.org/10.1038/onc.2011.541
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.
ISSN0950-9232
2011 Impact Factor: 6.373
2011 SCImago Journal Rankings: 1.216
DOIhttp://dx.doi.org/10.1038/onc.2011.541
PubMed Central IDPMC3426851
DC Field
Value
dc.contributor.authorLi, L
dc.contributor.authorYing, J
dc.contributor.authorLi, H
dc.contributor.authorZhang, Y
dc.contributor.authorShu, X
dc.contributor.authorFan, Y
dc.contributor.authorTan, J
dc.contributor.authorCao, Y
dc.contributor.authorTsao, SW
dc.contributor.authorSrivastava, G
dc.contributor.authorChan, ATC
dc.contributor.authorTao, Q
dc.date.accessioned2012-05-29T06:14:31Z
dc.date.available2012-05-29T06:14:31Z
dc.date.issued2011
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.
dc.description.naturelink_to_OA_fulltext
dc.identifier.citationOncogene, 2011, v. 31 n. 34, p. 3901-3912 [How to Cite?]
DOI: http://dx.doi.org/10.1038/onc.2011.541
dc.identifier.doihttp://dx.doi.org/10.1038/onc.2011.541
dc.identifier.epage3912
dc.identifier.hkuros207508
dc.identifier.issn0950-9232
2011 Impact Factor: 6.373
2011 SCImago Journal Rankings: 1.216
dc.identifier.issue34
dc.identifier.pmcidPMC3426851
dc.identifier.pmid22139084
dc.identifier.scopuseid_2-s2.0-84865417923
dc.identifier.spage3901
dc.identifier.urihttp://hdl.handle.net/10722/148663
dc.identifier.volume31
dc.languageeng
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
dc.publisher.placeUnited Kingdom
dc.relation.ispartofOncogene
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 carcinomas
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong
  2. Beijing Cancer Hospital
  3. Johns Hopkins Singapore
  4. Central South University China
  5. Chinese University of Hong Kong