Article: Aberrant activation of hedgehog signaling pathway in ovarian cancers: Effect on prognosis, cell invasion and differentiation

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TitleAberrant activation of hedgehog signaling pathway in ovarian cancers: Effect on prognosis, cell invasion and differentiation
AuthorsLiao, X1
Siu, MKY1
Au, CWH1
Wong, ESY1
Chan, HY1
Ip, PPC1
Ngan, HYS1
Cheung, ANY1
Issue Date2009
PublisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
CitationCarcinogenesis, 2009, v. 30 n. 1, p. 131-140 [How to Cite?]
DOI: http://dx.doi.org/10.1093/carcin/bgn230
AbstractAberrant activation of hedgehog (HH) pathway has been implicated in the development of human malignancies. This study aimed at investigating the role of HH molecules in human ovarian carcinogenesis. The expression profiles of HH molecules were examined in ovarian tumor samples and ovarian cancer cell lines and the in vitro effects of HH molecules on cell proliferation, apoptosis, migration, invasion and cell differentiation as well as related downstream target genes were assessed. Overexpression of Patched and Gli1 protein in ovarian cancers correlated with poor survival of the patients (P = 0.008; P = 0.004). Significantly elevated expression of Sonic hedgehog messenger RNA was observed in ovarian cancers compared with normal tissues and benign ovarian tumors and such differential expression was specific to histological types (P < 0.05). Ectopic Gli1 overexpression in ovarian cancer cells conferred increased cell proliferation, cell mobility, invasiveness and change in differentiation in association with increased expression of E-cadherin, vimentin, Bcl-2, caspases as well as β1 integrin, membrane type 1 matrix metalloproteinase (MT1-MMP) and vascular endothelial growth factor (VEGF). Treatment with 3-keto-N-(aminoethyl-aminocaproyl-dihydrocinnamoyl)-cyclopamine induced cancer cell apoptosis, suppressed cell growth, mobility and invasiveness and induced cancer cell dedifferentiation with decreased expression of E-cadherin, cytokeratin 7, Snail, calretinin, vimentin, Bcl-2, caspases, β1 integrin, MT1-MMP and VEGF. Our data suggested that abnormal HH signaling activation plays important roles in the development and progression of ovarian cancers. Gli1 expression is an independent prognostic marker. Inhibition of the HH pathway molecules might be a valid therapeutic strategy for ovarian cancers. © The Author 2008. Published by Oxford University Press. All rights reserved.
ISSN0143-3334
2011 Impact Factor: 5.702
2011 SCImago Journal Rankings: 0.692
DOIhttp://dx.doi.org/10.1093/carcin/bgn230
ISI Accession Number IDWOS:000262718300018
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorLiao, X
dc.contributor.authorSiu, MKY
dc.contributor.authorAu, CWH
dc.contributor.authorWong, ESY
dc.contributor.authorChan, HY
dc.contributor.authorIp, PPC
dc.contributor.authorNgan, HYS
dc.contributor.authorCheung, ANY
dc.date.accessioned2010-05-31T04:09:15Z
dc.date.available2010-05-31T04:09:15Z
dc.date.issued2009
dc.description.abstractAberrant activation of hedgehog (HH) pathway has been implicated in the development of human malignancies. This study aimed at investigating the role of HH molecules in human ovarian carcinogenesis. The expression profiles of HH molecules were examined in ovarian tumor samples and ovarian cancer cell lines and the in vitro effects of HH molecules on cell proliferation, apoptosis, migration, invasion and cell differentiation as well as related downstream target genes were assessed. Overexpression of Patched and Gli1 protein in ovarian cancers correlated with poor survival of the patients (P = 0.008; P = 0.004). Significantly elevated expression of Sonic hedgehog messenger RNA was observed in ovarian cancers compared with normal tissues and benign ovarian tumors and such differential expression was specific to histological types (P < 0.05). Ectopic Gli1 overexpression in ovarian cancer cells conferred increased cell proliferation, cell mobility, invasiveness and change in differentiation in association with increased expression of E-cadherin, vimentin, Bcl-2, caspases as well as β1 integrin, membrane type 1 matrix metalloproteinase (MT1-MMP) and vascular endothelial growth factor (VEGF). Treatment with 3-keto-N-(aminoethyl-aminocaproyl-dihydrocinnamoyl)-cyclopamine induced cancer cell apoptosis, suppressed cell growth, mobility and invasiveness and induced cancer cell dedifferentiation with decreased expression of E-cadherin, cytokeratin 7, Snail, calretinin, vimentin, Bcl-2, caspases, β1 integrin, MT1-MMP and VEGF. Our data suggested that abnormal HH signaling activation plays important roles in the development and progression of ovarian cancers. Gli1 expression is an independent prognostic marker. Inhibition of the HH pathway molecules might be a valid therapeutic strategy for ovarian cancers. © The Author 2008. Published by Oxford University Press. All rights reserved.
dc.description.naturelink_to_subscribed_fulltext
dc.identifier.citationCarcinogenesis, 2009, v. 30 n. 1, p. 131-140 [How to Cite?]
DOI: http://dx.doi.org/10.1093/carcin/bgn230
dc.identifier.doihttp://dx.doi.org/10.1093/carcin/bgn230
dc.identifier.epage140
dc.identifier.hkuros166975
dc.identifier.isiWOS:000262718300018
dc.identifier.issn0143-3334
2011 Impact Factor: 5.702
2011 SCImago Journal Rankings: 0.692
dc.identifier.issue1
dc.identifier.openurl
dc.identifier.pmid19028702
dc.identifier.scopuseid_2-s2.0-58949100355
dc.identifier.spage131
dc.identifier.urihttp://hdl.handle.net/10722/60368
dc.identifier.volume30
dc.languageeng
dc.publisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
dc.publisher.placeUnited Kingdom
dc.relation.ispartofCarcinogenesis
dc.relation.referencesReferences in Scopus
dc.rightsCarcinogenesis. Copyright © Lippincott Williams & Wilkins.
dc.subject.meshCell Differentiation
dc.subject.meshCell Line, Tumor
dc.subject.meshFemale
dc.subject.meshHedgehog Proteins - metabolism
dc.subject.meshHumans
dc.subject.meshImmunohistochemistry
dc.subject.meshNeoplasm Invasiveness
dc.subject.meshOvarian Neoplasms - metabolism - pathology
dc.subject.meshPrognosis
dc.subject.meshReceptors, Cell Surface - metabolism
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction
dc.subject.meshSignal Transduction
dc.subject.meshTranscription Factors - metabolism
dc.titleAberrant activation of hedgehog signaling pathway in ovarian cancers: Effect on prognosis, cell invasion and differentiation
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong