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Article: p70 S6 kinase promotes epithelial to mesenchymal transition through snail induction in ovarian cancer cells
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Titlep70 S6 kinase promotes epithelial to mesenchymal transition through snail induction in ovarian cancer cells
 
AuthorsPon, YL1
Zhou, HY1
Cheung, ANY1
Ngan, HYS1
Wong, AST1
 
Issue Date2008
 
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
 
CitationCancer Research, 2008, v. 68 n. 16, p. 6524-6532 [How to Cite?]
DOI: http://dx.doi.org/10.1158/0008-5472.CAN-07-6302
 
Abstractp70 S6 kinase (p70 S6K) is a downstream effector of phosphatidylinositol 3-kinase and is frequently activated in human ovarian cancer. Here we show that p70 S6K functions in epithelial to mesenchymal transition (EMT) responsible for the acquisition of invasiveness during tumor progression. This tumorigenic activity is associated with the ability of p70 S6K to repress E-cadherin through the up-regulation of Snail. p70 S6K activation induced phenotypic changes consistent with EMT in ovarian cancer cells: The cells lost epithelial cell morphology, acquired fibroblast-like properties, and showed reduced intercellular adhesion. Western blot showed that p70 S6K activation led to decreased expression of the epithelial marker E-cadherin and increased expression of mesenchymal markers N-cadherin and vimentin. Inhibition of p70 S6K by a specific inhibitor or small interfering RNA reversed the shift of EMT markers. Importantly, p70 S6K activation also stimulated the expression of Snail, a repressor of E-cadherin and an inducer of EMT, but not other family members such as Slug. This induction of Snail was regulated at multiple levels by increasing transcription, inhibiting protein degradation, and enhancing nuclear localization of Snail. RNA interferencemediated knockdown of Snail suppressed p70 S6K-induced EMT, confirming that the effect was Snail specific. Furthermore, phospho (active)-p70 S6K staining correlated with higher tumor grade. We also showed a significant positive correlation between p70 S6K activation and Snail expression in ovarian cancer tissues. These results indicate that p70 S6K may play a critical role in tumor progression in ovarian cancer through the induction of EMT. Targeting p70 S6K may thus be a useful strategy to impede cancer cell invasion and metastasis. © 2008 American Association for Cancer Research.
 
ISSN0008-5472
2013 Impact Factor: 9.284
2013 SCImago Journal Rankings: 5.627
 
DOIhttp://dx.doi.org/10.1158/0008-5472.CAN-07-6302
 
ISI Accession Number IDWOS:000258548200008
Funding AgencyGrant Number
Hong Kong Research Grants Council7599/05M
Funding Information:

Grant support: Hong Kong Research Grants Council Grant 7599/05M (A.S.T. Wong).

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorPon, YL
 
dc.contributor.authorZhou, HY
 
dc.contributor.authorCheung, ANY
 
dc.contributor.authorNgan, HYS
 
dc.contributor.authorWong, AST
 
dc.date.accessioned2010-05-31T04:08:44Z
 
dc.date.available2010-05-31T04:08:44Z
 
dc.date.issued2008
 
dc.description.abstractp70 S6 kinase (p70 S6K) is a downstream effector of phosphatidylinositol 3-kinase and is frequently activated in human ovarian cancer. Here we show that p70 S6K functions in epithelial to mesenchymal transition (EMT) responsible for the acquisition of invasiveness during tumor progression. This tumorigenic activity is associated with the ability of p70 S6K to repress E-cadherin through the up-regulation of Snail. p70 S6K activation induced phenotypic changes consistent with EMT in ovarian cancer cells: The cells lost epithelial cell morphology, acquired fibroblast-like properties, and showed reduced intercellular adhesion. Western blot showed that p70 S6K activation led to decreased expression of the epithelial marker E-cadherin and increased expression of mesenchymal markers N-cadherin and vimentin. Inhibition of p70 S6K by a specific inhibitor or small interfering RNA reversed the shift of EMT markers. Importantly, p70 S6K activation also stimulated the expression of Snail, a repressor of E-cadherin and an inducer of EMT, but not other family members such as Slug. This induction of Snail was regulated at multiple levels by increasing transcription, inhibiting protein degradation, and enhancing nuclear localization of Snail. RNA interferencemediated knockdown of Snail suppressed p70 S6K-induced EMT, confirming that the effect was Snail specific. Furthermore, phospho (active)-p70 S6K staining correlated with higher tumor grade. We also showed a significant positive correlation between p70 S6K activation and Snail expression in ovarian cancer tissues. These results indicate that p70 S6K may play a critical role in tumor progression in ovarian cancer through the induction of EMT. Targeting p70 S6K may thus be a useful strategy to impede cancer cell invasion and metastasis. © 2008 American Association for Cancer Research.
 
dc.description.naturelink_to_OA_fulltext
 
dc.identifier.citationCancer Research, 2008, v. 68 n. 16, p. 6524-6532 [How to Cite?]
DOI: http://dx.doi.org/10.1158/0008-5472.CAN-07-6302
 
dc.identifier.citeulike6185080
 
dc.identifier.doihttp://dx.doi.org/10.1158/0008-5472.CAN-07-6302
 
dc.identifier.eissn1538-7445
 
dc.identifier.epage6532
 
dc.identifier.hkuros163467
 
dc.identifier.hkuros144168
 
dc.identifier.isiWOS:000258548200008
Funding AgencyGrant Number
Hong Kong Research Grants Council7599/05M
Funding Information:

Grant support: Hong Kong Research Grants Council Grant 7599/05M (A.S.T. Wong).

 
dc.identifier.issn0008-5472
2013 Impact Factor: 9.284
2013 SCImago Journal Rankings: 5.627
 
dc.identifier.issue16
 
dc.identifier.openurl
 
dc.identifier.pmid18701475
 
dc.identifier.scopuseid_2-s2.0-53049108469
 
dc.identifier.spage6524
 
dc.identifier.urihttp://hdl.handle.net/10722/60343
 
dc.identifier.volume68
 
dc.languageeng
 
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofCancer Research
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshCell Differentiation
 
dc.subject.meshEpithelial Cells - metabolism - pathology
 
dc.subject.meshMesoderm - metabolism - pathology
 
dc.subject.meshOvarian Neoplasms - genetics - metabolism - pathology
 
dc.subject.meshRibosomal Protein S6 Kinases, 70-kDa - physiology
 
dc.titlep70 S6 kinase promotes epithelial to mesenchymal transition through snail induction in ovarian cancer cells
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong