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Article: Aberrant activation of ERK/FOXM1 signaling cascade triggers the cell migration/invasion in ovarian cancer cells

TitleAberrant activation of ERK/FOXM1 signaling cascade triggers the cell migration/invasion in ovarian cancer cells
Authors
KeywordsForkhead transcription factor
Cell migration
Cancer cell
Carcinogenesis
Ovary cancer
Issue Date2011
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2011, v. 6 n. 8 How to Cite?
AbstractForkhead box M1 (FOXM1) is a proliferation-associated transcription factor essential for cell cycle progression. Numerous studies have documented that FOXM1 has multiple functions in tumorigenesis and its elevated levels are frequently associated with cancer progression. Here, we characterized the role of ERK/FOXM1 signaling in mediating the metastatic potential of ovarian cancer cells. Immunohistochemical (IHC), immunoblotting and semi-quantitative RT-PCR analyses found that both phospho-ERK and FOXM1 were frequently upregulated in ovarian cancers. Intriguingly, the overexpressed phospho-ERK (p<0.001) and FOXM1 (p<0.001) were significantly correlated to high-grade ovarian tumors with aggressive behavior such as metastasized lymph node (5 out of 6). Moreover, the expressions of phospho-ERK and FOXM1 had significantly positive correlation (p<0.001). Functionally, ectopic expression of FOXM1B remarkably enhanced cell migration/invasion, while FOXM1C not only increased cell proliferation but also promoted cell migration/invasion. Conversely, inhibition of FOXM1 expression by either thiostrepton or U0126 could significantly impair FOXM1 mediated oncogenic capacities. However, the down-regulation of FOXM1 by either thiostrepton or U0126 required the presence of p53 in ovarian cancer cells. Collectively, our data suggest that over-expression of FOXM1 might stem from the constitutively active ERK which confers the metastatic capabilities to ovarian cancer cells. The impairment of metastatic potential of cancer cells by FOXM1 inhibitors underscores its therapeutic value in advanced ovarian tumors. © 2011 Lok et al.
Persistent Identifierhttp://hdl.handle.net/10722/138965
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Wong Cheuk She Charitable Foundation
Funding Information:

This study was supported by the Wong Cheuk She Charitable Foundation. This support is from private donations, and no funder's website is available. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

 

DC FieldValueLanguage
dc.contributor.authorLok, GTMen_HK
dc.contributor.authorChan, DWen_HK
dc.contributor.authorLiu, VWSen_HK
dc.contributor.authorHui, WWYen_HK
dc.contributor.authorLeung, THYen_HK
dc.contributor.authorYao, KMen_HK
dc.contributor.authorNgan, HYSen_HK
dc.date.accessioned2011-09-23T05:43:14Z-
dc.date.available2011-09-23T05:43:14Z-
dc.date.issued2011en_HK
dc.identifier.citationPlos One, 2011, v. 6 n. 8en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/138965-
dc.description.abstractForkhead box M1 (FOXM1) is a proliferation-associated transcription factor essential for cell cycle progression. Numerous studies have documented that FOXM1 has multiple functions in tumorigenesis and its elevated levels are frequently associated with cancer progression. Here, we characterized the role of ERK/FOXM1 signaling in mediating the metastatic potential of ovarian cancer cells. Immunohistochemical (IHC), immunoblotting and semi-quantitative RT-PCR analyses found that both phospho-ERK and FOXM1 were frequently upregulated in ovarian cancers. Intriguingly, the overexpressed phospho-ERK (p<0.001) and FOXM1 (p<0.001) were significantly correlated to high-grade ovarian tumors with aggressive behavior such as metastasized lymph node (5 out of 6). Moreover, the expressions of phospho-ERK and FOXM1 had significantly positive correlation (p<0.001). Functionally, ectopic expression of FOXM1B remarkably enhanced cell migration/invasion, while FOXM1C not only increased cell proliferation but also promoted cell migration/invasion. Conversely, inhibition of FOXM1 expression by either thiostrepton or U0126 could significantly impair FOXM1 mediated oncogenic capacities. However, the down-regulation of FOXM1 by either thiostrepton or U0126 required the presence of p53 in ovarian cancer cells. Collectively, our data suggest that over-expression of FOXM1 might stem from the constitutively active ERK which confers the metastatic capabilities to ovarian cancer cells. The impairment of metastatic potential of cancer cells by FOXM1 inhibitors underscores its therapeutic value in advanced ovarian tumors. © 2011 Lok et al.en_HK
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_HK
dc.relation.ispartofPLoS ONEen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectForkhead transcription factor-
dc.subjectCell migration-
dc.subjectCancer cell-
dc.subjectCarcinogenesis-
dc.subjectOvary cancer-
dc.titleAberrant activation of ERK/FOXM1 signaling cascade triggers the cell migration/invasion in ovarian cancer cellsen_HK
dc.typeArticleen_HK
dc.identifier.emailChan, DW: dwchan@hku.hken_HK
dc.identifier.emailLiu, VWS: vwsliu@hkusua.hku.hken_HK
dc.identifier.emailYao, KM: kmyao@hku.hken_HK
dc.identifier.emailNgan, HYS: hysngan@hkucc.hku.hken_HK
dc.identifier.authorityChan, DW=rp00543en_HK
dc.identifier.authorityLiu, VWS=rp00341en_HK
dc.identifier.authorityYao, KM=rp00344en_HK
dc.identifier.authorityNgan, HYS=rp00346en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0023790en_HK
dc.identifier.pmid21858223-
dc.identifier.pmcidPMC3157468-
dc.identifier.scopuseid_2-s2.0-80051723542en_HK
dc.identifier.hkuros194105en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80051723542&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume6en_HK
dc.identifier.issue8en_HK
dc.identifier.spagee23790en_US
dc.identifier.epagee23790en_US
dc.identifier.isiWOS:000294121300095-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLok, GTM=44161157700en_HK
dc.identifier.scopusauthoridChan, DW=26533900600en_HK
dc.identifier.scopusauthoridLiu, VWS=7006405113en_HK
dc.identifier.scopusauthoridHui, WWY=50261742400en_HK
dc.identifier.scopusauthoridLeung, THY=7202110922en_HK
dc.identifier.scopusauthoridYao, KM=7403234578en_HK
dc.identifier.scopusauthoridNgan, HYS=34571944100en_HK

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