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Article: Stem cell transcription factor NANOG controls cell migration and invasion via dysregulation of E-cadherin and FoxJ1 and contributes to adverse clinical outcome in ovarian cancers

TitleStem cell transcription factor NANOG controls cell migration and invasion via dysregulation of E-cadherin and FoxJ1 and contributes to adverse clinical outcome in ovarian cancers
Authors
KeywordsNANOG
Cell migration and invasion
Prognostic marker
Therapeutic molecular target
Ovarian cancer
Issue Date2013
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2013, v. 32 n. 30, p. 3500-3509 How to Cite?
Abstract
Ovarian cancer is the most lethal of all gynecological malignancies, and the identification of novel prognostic and therapeutic targets for ovarian cancer is crucial. It is believed that only a small subset of cancer cells are endowed with stem cell properties, which are responsible for tumor growth, metastatic progression and recurrence. NANOG is one of the key transcription factors essential for maintaining self-renewal and pluripotency in stem cells. This study investigated the role of NANOG in ovarian carcinogenesis and showed overexpression of NANOG mRNA and protein in the nucleus of ovarian cancers compared with benign ovarian lesions. Increased nuclear NANOG expression was significantly associated with high-grade cancers, serous histological subtypes, reduced chemosensitivity, and poor overall and disease-free survival. Further analysis showed NANOG is an independent prognostic factor for overall and disease-free survival. Moreover, NANOG was highly expressed in ovarian cancer cell lines with metastasis-associated property and in clinical samples of metastatic foci. Stable knockdown of NANOG impeded ovarian cancer cell proliferation, migration and invasion, which was accompanied by an increase in mRNA expression of E-cadherin, caveolin-1, FOXO1, FOXO3a, FOXJ1 and FOXB1. Conversely, ectopic NANOG overexpression enhanced ovarian cancer cell migration and invasion along with decreased E-cadherin, caveolin-1, FOXO1, FOXO3a, FOXJ1 and FOXB1 mRNA expression. Importantly, we found Nanog-mediated cell migration and invasion involved its regulation of E-cadherin and FOXJ1. This is the first report revealing the association between NANOG expression and clinical outcome of patients with ovarian cancers, suggesting NANOG to be a potential prognostic marker and therapeutic molecular target in ovarian cancer.Oncogene advance online publication, 3 September 2012; doi:10.1038/onc.2012.363.
Persistent Identifierhttp://hdl.handle.net/10722/169290
ISSN
2013 Impact Factor: 8.559
2013 SCImago Journal Rankings: 4.764
ISI Accession Number ID

 

Author Affiliations
  1. The University of Hong Kong
  2. Imperial College London
  3. University of Texas M. D. Anderson Cancer Center
DC FieldValueLanguage
dc.contributor.authorSiu, MKYen_US
dc.contributor.authorWong, ESYen_US
dc.contributor.authorKong, DSHen_US
dc.contributor.authorChan, HYen_US
dc.contributor.authorJiang, Len_US
dc.contributor.authorWong, OGWen_US
dc.contributor.authorLam, EWFen_US
dc.contributor.authorChan, KKLen_US
dc.contributor.authorNgan, HYSen_US
dc.contributor.authorLe, XFen_US
dc.contributor.authorCheung, ANen_US
dc.date.accessioned2012-10-18T08:49:17Z-
dc.date.available2012-10-18T08:49:17Z-
dc.date.issued2013en_US
dc.identifier.citationOncogene, 2013, v. 32 n. 30, p. 3500-3509en_US
dc.identifier.issn0950-9232-
dc.identifier.urihttp://hdl.handle.net/10722/169290-
dc.description.abstractOvarian cancer is the most lethal of all gynecological malignancies, and the identification of novel prognostic and therapeutic targets for ovarian cancer is crucial. It is believed that only a small subset of cancer cells are endowed with stem cell properties, which are responsible for tumor growth, metastatic progression and recurrence. NANOG is one of the key transcription factors essential for maintaining self-renewal and pluripotency in stem cells. This study investigated the role of NANOG in ovarian carcinogenesis and showed overexpression of NANOG mRNA and protein in the nucleus of ovarian cancers compared with benign ovarian lesions. Increased nuclear NANOG expression was significantly associated with high-grade cancers, serous histological subtypes, reduced chemosensitivity, and poor overall and disease-free survival. Further analysis showed NANOG is an independent prognostic factor for overall and disease-free survival. Moreover, NANOG was highly expressed in ovarian cancer cell lines with metastasis-associated property and in clinical samples of metastatic foci. Stable knockdown of NANOG impeded ovarian cancer cell proliferation, migration and invasion, which was accompanied by an increase in mRNA expression of E-cadherin, caveolin-1, FOXO1, FOXO3a, FOXJ1 and FOXB1. Conversely, ectopic NANOG overexpression enhanced ovarian cancer cell migration and invasion along with decreased E-cadherin, caveolin-1, FOXO1, FOXO3a, FOXJ1 and FOXB1 mRNA expression. Importantly, we found Nanog-mediated cell migration and invasion involved its regulation of E-cadherin and FOXJ1. This is the first report revealing the association between NANOG expression and clinical outcome of patients with ovarian cancers, suggesting NANOG to be a potential prognostic marker and therapeutic molecular target in ovarian cancer.Oncogene advance online publication, 3 September 2012; doi:10.1038/onc.2012.363.-
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc-
dc.relation.ispartofOncogeneen_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectNANOG-
dc.subjectCell migration and invasion-
dc.subjectPrognostic marker-
dc.subjectTherapeutic molecular target-
dc.subjectOvarian cancer-
dc.titleStem cell transcription factor NANOG controls cell migration and invasion via dysregulation of E-cadherin and FoxJ1 and contributes to adverse clinical outcome in ovarian cancersen_US
dc.typeArticleen_US
dc.identifier.emailSiu, MKY: mkysiu@hkucc.hku.hken_US
dc.identifier.emailWong, ESY: esywong@hkucc.hku.hken_US
dc.identifier.emailWong, OGW: wonggw@hkucc.hku.hken_US
dc.identifier.emailChan, KKL: karenchan@pobox.comen_US
dc.identifier.emailNgan, HYS: hysngan@hkucc.hku.hk-
dc.identifier.emailCheung, AN: anycheun@hkucc.hku.hk-
dc.identifier.authorityNgan, HYS=rp00346en_US
dc.identifier.authorityCheung, ANY=rp00542en_US
dc.description.naturepostprint-
dc.identifier.doi10.1038/onc.2012.363-
dc.identifier.pmid22945654-
dc.identifier.scopuseid_2-s2.0-84880923339-
dc.identifier.hkuros212017en_US
dc.identifier.hkuros220587-
dc.identifier.isiWOS:000322220800003-
dc.publisher.placeUnited Kingdom-

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