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Article: Cadherin switching and activation of p120 catenin signaling are mediators of gonadotropin-releasing hormone to promote tumor cell migration and invasion in ovarian cancer

TitleCadherin switching and activation of p120 catenin signaling are mediators of gonadotropin-releasing hormone to promote tumor cell migration and invasion in ovarian cancer
Authors
KeywordsCadherin
GnRH
Motility
Ovarian cancer
P120ctn
Issue Date2010
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2010, v. 29 n. 16, p. 2427-2440 How to Cite?
AbstractGonadotropin-releasing hormone (GnRH) receptor expression is often elevated in ovarian cancer, but its potential role in ovarian cancer metastasis has just begun to be revealed. Cadherin switching is a crucial step during tumorigenesis, particularly in metastasis. Here, we showed that GnRH is an inducer of E-to P-cadherin switching, which is reminiscent of that seen during ovarian tumor progression. Overexpression of P-cadherin significantly enhanced, whereas knockdown of P-cadherin reduced migration and invasion regardless of E-cadherin expression, suggesting that inappropriate expression of P-cadherin contributes to the invasive phenotype. These effects of P-cadherin were mediated by activation of the Rho GTPases, Rac1, and Cdc42, through accumulation of p120 catenin (p120 ctn) in the cytoplasm. The use of p120 ctn small interfering RNA or chimeric cadherin construct to inhibit p120 ctn expression and cytoplasmic localization, respectively, resulted in significant inhibition of cell migration and invasion, with a concomitant reduction in Rac1 and Cdc42 activation, confirming that the effect was p120 ctn specific. Similarly, the migratory/invasive phenotype could be reversed by expression of dominant-negative Rac1 and Cdc42. These results identify for the first time cadherin switching and p120 ctn signaling as important targets of GnRH function and as novel mediators of invasiveness and tumor progression in ovarian cancer. © 2010 Macmillan Publishers Limited All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/127449
ISSN
2015 Impact Factor: 7.932
2015 SCImago Journal Rankings: 4.047
ISI Accession Number ID
Funding AgencyGrant Number
Canadian Institutes of Health
Hong Kong Research Grant Council778108
HKU
Funding Information:

We thank Drs N Auersperg, A Hall, and C Gottardi for cell lines and plasmids. This work was supported by Canadian Institutes of Health Research grant (PCK Leung), and by Hong Kong Research Grant Council Grant 778108 and HKU Outstanding Young Researcher Award (AST Wong).

References

 

DC FieldValueLanguage
dc.contributor.authorCheung, LWTen_HK
dc.contributor.authorLeung, PCKen_HK
dc.contributor.authorWong, ASTen_HK
dc.date.accessioned2010-10-31T13:26:13Z-
dc.date.available2010-10-31T13:26:13Z-
dc.date.issued2010en_HK
dc.identifier.citationOncogene, 2010, v. 29 n. 16, p. 2427-2440en_HK
dc.identifier.issn0950-9232en_HK
dc.identifier.urihttp://hdl.handle.net/10722/127449-
dc.description.abstractGonadotropin-releasing hormone (GnRH) receptor expression is often elevated in ovarian cancer, but its potential role in ovarian cancer metastasis has just begun to be revealed. Cadherin switching is a crucial step during tumorigenesis, particularly in metastasis. Here, we showed that GnRH is an inducer of E-to P-cadherin switching, which is reminiscent of that seen during ovarian tumor progression. Overexpression of P-cadherin significantly enhanced, whereas knockdown of P-cadherin reduced migration and invasion regardless of E-cadherin expression, suggesting that inappropriate expression of P-cadherin contributes to the invasive phenotype. These effects of P-cadherin were mediated by activation of the Rho GTPases, Rac1, and Cdc42, through accumulation of p120 catenin (p120 ctn) in the cytoplasm. The use of p120 ctn small interfering RNA or chimeric cadherin construct to inhibit p120 ctn expression and cytoplasmic localization, respectively, resulted in significant inhibition of cell migration and invasion, with a concomitant reduction in Rac1 and Cdc42 activation, confirming that the effect was p120 ctn specific. Similarly, the migratory/invasive phenotype could be reversed by expression of dominant-negative Rac1 and Cdc42. These results identify for the first time cadherin switching and p120 ctn signaling as important targets of GnRH function and as novel mediators of invasiveness and tumor progression in ovarian cancer. © 2010 Macmillan Publishers Limited All rights reserved.en_HK
dc.languageengen_HK
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/oncen_HK
dc.relation.ispartofOncogeneen_HK
dc.subjectCadherinen_HK
dc.subjectGnRHen_HK
dc.subjectMotilityen_HK
dc.subjectOvarian canceren_HK
dc.subjectP120ctnen_HK
dc.subject.meshCadherins - physiology-
dc.subject.meshCatenins - physiology-
dc.subject.meshGonadotropin-Releasing Hormone - physiology-
dc.subject.meshOvarian Neoplasms - pathology-
dc.subject.meshSignal Transduction - physiology-
dc.titleCadherin switching and activation of p120 catenin signaling are mediators of gonadotropin-releasing hormone to promote tumor cell migration and invasion in ovarian canceren_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0950-9232&volume=29&issue=16&spage=2427&epage=2440&date=2010&atitle=Cadherin+switching+and+activation+of+p120+catenin+signaling+are+mediators+of+gonadotropin-releasing+hormone+to+promote+tumor+cell+migration+and+invasion+in+ovarian+canceren_HK
dc.identifier.emailWong, AST: awong1@hkucc.hku.hken_HK
dc.identifier.authorityWong, AST=rp00805en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/onc.2009.523en_HK
dc.identifier.pmid20118984-
dc.identifier.scopuseid_2-s2.0-77951620350en_HK
dc.identifier.hkuros174118en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77951620350&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume29en_HK
dc.identifier.issue16en_HK
dc.identifier.spage2427en_HK
dc.identifier.epage2440en_HK
dc.identifier.eissn1476-5594-
dc.identifier.isiWOS:000276951500011-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridCheung, LWT=14119560800en_HK
dc.identifier.scopusauthoridLeung, PCK=12782513900en_HK
dc.identifier.scopusauthoridWong, AST=23987963300en_HK
dc.identifier.citeulike6614798-

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