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Article: p70 S6 kinase drives ovarian cancer metastasis through multicellular spheroid-peritoneum interaction and P-cadherin/β1 integrin signaling activation

Titlep70 S6 kinase drives ovarian cancer metastasis through multicellular spheroid-peritoneum interaction and P-cadherin/β1 integrin signaling activation
Authors
Issue Date2014
PublisherImpact Journals LLC. The Journal's web site is located at http://www.impactjournals.com/oncotarget/index.html
Citation
Oncotarget, 2014, v. 5 n. 19, p. 9133-9149 How to Cite?
AbstractPeritoneal dissemination as a manifestation of ovarian cancer is an adverse prognostic factor associated with poor clinical outcome, and is thus a potentially promising target for improved treatment. Sphere forming cells (multicellular spheroids) present in malignant ascites of patients with ovarian cancer represent a major impediment to effective treatment. p70 S6 kinase (p70S6K), which is a downstream effector of mammalian target of rapamycin, is frequently hyperactivated in human ovarian cancer. Here, we identified p70S6K as an important regulator for the seeding and successful colonization of ovarian cancer spheroids on the peritoneum. Furthermore, we provided evidence for the existence of a novel crosstalk between P-cadherin and β1 integrin, which was crucial for the high degree of specificity in cell adhesion. In particular, we demonstrated that the upregulation of mature β1 integrin occurred as a consequence of P-cadherin expression through the induction of the Golgi glycosyltransferase, ST6Gal-I, which mediated β1 integrin hypersialylation. Loss of p70S6K or targeting the P-cadherin/β1-integrin interplay could significantly attenuate the metastatic spread onto the peritoneum in vivo. These findings establish a new role for p70S6K in tumor spheroid-mesothelium communication in ovarian cancer and provide a preclinical rationale for targeting p70S6K as a new avenue for microenvironment-based therapeutic strategy.
Persistent Identifierhttp://hdl.handle.net/10722/202507
ISSN
2015 Impact Factor: 5.008
2015 SCImago Journal Rankings: 2.294
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorIp, KM-
dc.contributor.authorYung, SSY-
dc.contributor.authorChan, DTM-
dc.contributor.authorTsao, GSW-
dc.contributor.authorWong, AST-
dc.date.accessioned2014-09-19T08:08:28Z-
dc.date.available2014-09-19T08:08:28Z-
dc.date.issued2014-
dc.identifier.citationOncotarget, 2014, v. 5 n. 19, p. 9133-9149-
dc.identifier.issn1949-2553-
dc.identifier.urihttp://hdl.handle.net/10722/202507-
dc.description.abstractPeritoneal dissemination as a manifestation of ovarian cancer is an adverse prognostic factor associated with poor clinical outcome, and is thus a potentially promising target for improved treatment. Sphere forming cells (multicellular spheroids) present in malignant ascites of patients with ovarian cancer represent a major impediment to effective treatment. p70 S6 kinase (p70S6K), which is a downstream effector of mammalian target of rapamycin, is frequently hyperactivated in human ovarian cancer. Here, we identified p70S6K as an important regulator for the seeding and successful colonization of ovarian cancer spheroids on the peritoneum. Furthermore, we provided evidence for the existence of a novel crosstalk between P-cadherin and β1 integrin, which was crucial for the high degree of specificity in cell adhesion. In particular, we demonstrated that the upregulation of mature β1 integrin occurred as a consequence of P-cadherin expression through the induction of the Golgi glycosyltransferase, ST6Gal-I, which mediated β1 integrin hypersialylation. Loss of p70S6K or targeting the P-cadherin/β1-integrin interplay could significantly attenuate the metastatic spread onto the peritoneum in vivo. These findings establish a new role for p70S6K in tumor spheroid-mesothelium communication in ovarian cancer and provide a preclinical rationale for targeting p70S6K as a new avenue for microenvironment-based therapeutic strategy.-
dc.languageeng-
dc.publisherImpact Journals LLC. The Journal's web site is located at http://www.impactjournals.com/oncotarget/index.html-
dc.relation.ispartofOncotarget-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titlep70 S6 kinase drives ovarian cancer metastasis through multicellular spheroid-peritoneum interaction and P-cadherin/β1 integrin signaling activation-
dc.typeArticle-
dc.identifier.emailIp, KM: carmanip@hku.hk-
dc.identifier.emailYung, SSY: ssyyung@hku.hk-
dc.identifier.emailChan, DTM: dtmchan@hku.hk-
dc.identifier.emailTsao, GSW: gswtsao@hku.hk-
dc.identifier.emailWong, AST: awong1@hku.hk-
dc.identifier.authorityYung, SSY=rp00455-
dc.identifier.authorityChan, DTM=rp00394-
dc.identifier.authorityTsao, GSW=rp00399-
dc.identifier.authorityWong, AST=rp00805-
dc.description.naturepublished_or_final_version-
dc.identifier.pmid25193855-
dc.identifier.pmcidPMC4253424-
dc.identifier.scopuseid_2-s2.0-84910070048-
dc.identifier.hkuros239749-
dc.identifier.volume5-
dc.identifier.issue19-
dc.identifier.spage9133-
dc.identifier.epage9149-
dc.identifier.isiWOS:000348033800025-
dc.publisher.placeUnited States-

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