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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
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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, J5 3
Li, H5
Zhang, Y5
Shu, X5
Fan, Y5
Tan, J2
Cao, Y4
Tsao, SW1
Srivastava, G1
Chan, ATC5
Tao, Q5
 
Issue Date2012
 
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
 
CitationOncogene, 2012, 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
2012 Impact Factor: 7.357
2012 SCImago Journal Rankings: 3.558
 
DOIhttp://dx.doi.org/10.1038/onc.2011.541
 
PubMed Central IDPMC3426851
 
DC FieldValue
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.issued2012
 
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, 2012, 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.hkuros217742
 
dc.identifier.issn0950-9232
2012 Impact Factor: 7.357
2012 SCImago Journal Rankings: 3.558
 
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
 
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<contributor.author>Shu, X</contributor.author>
<contributor.author>Fan, Y</contributor.author>
<contributor.author>Tan, J</contributor.author>
<contributor.author>Cao, Y</contributor.author>
<contributor.author>Tsao, SW</contributor.author>
<contributor.author>Srivastava, G</contributor.author>
<contributor.author>Chan, ATC</contributor.author>
<contributor.author>Tao, Q</contributor.author>
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<description.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.</description.abstract>
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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