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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
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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
 
AuthorsSiu, MKY1
Wong, ESY1
Kong, DSH1
Chan, HY1
Jiang, L1
Wong, OGW1
Lam, EWF2
Chan, KKL1
Ngan, HYS1
Le, XF3
Cheung, AN1
 
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
 
CitationOncogene, 2013, v. 32 n. 30, p. 3500-3509 [How to Cite?]
DOI: http://dx.doi.org/10.1038/onc.2012.363
 
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.
 
ISSN0950-9232
2012 Impact Factor: 7.357
2012 SCImago Journal Rankings: 3.558
 
DOIhttp://dx.doi.org/10.1038/onc.2012.363
 
DC FieldValue
dc.contributor.authorSiu, MKY
 
dc.contributor.authorWong, ESY
 
dc.contributor.authorKong, DSH
 
dc.contributor.authorChan, HY
 
dc.contributor.authorJiang, L
 
dc.contributor.authorWong, OGW
 
dc.contributor.authorLam, EWF
 
dc.contributor.authorChan, KKL
 
dc.contributor.authorNgan, HYS
 
dc.contributor.authorLe, XF
 
dc.contributor.authorCheung, AN
 
dc.date.accessioned2012-10-18T08:49:17Z
 
dc.date.available2012-10-18T08:49:17Z
 
dc.date.issued2013
 
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.description.naturepostprint
 
dc.identifier.citationOncogene, 2013, v. 32 n. 30, p. 3500-3509 [How to Cite?]
DOI: http://dx.doi.org/10.1038/onc.2012.363
 
dc.identifier.doihttp://dx.doi.org/10.1038/onc.2012.363
 
dc.identifier.hkuros212017
 
dc.identifier.hkuros220587
 
dc.identifier.issn0950-9232
2012 Impact Factor: 7.357
2012 SCImago Journal Rankings: 3.558
 
dc.identifier.pmid22945654
 
dc.identifier.scopuseid_2-s2.0-84880923339
 
dc.identifier.urihttp://hdl.handle.net/10722/169290
 
dc.languageeng
 
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofOncogene
 
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 cancers
 
dc.typeArticle
 
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<contributor.author>Wong, ESY</contributor.author>
<contributor.author>Kong, DSH</contributor.author>
<contributor.author>Chan, HY</contributor.author>
<contributor.author>Jiang, L</contributor.author>
<contributor.author>Wong, OGW</contributor.author>
<contributor.author>Lam, EWF</contributor.author>
<contributor.author>Chan, KKL</contributor.author>
<contributor.author>Ngan, HYS</contributor.author>
<contributor.author>Le, XF</contributor.author>
<contributor.author>Cheung, AN</contributor.author>
<date.accessioned>2012-10-18T08:49:17Z</date.accessioned>
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<description.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.</description.abstract>
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<subject>Therapeutic molecular target</subject>
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Author Affiliations
  1. The University of Hong Kong
  2. Imperial College London
  3. University of Texas M. D. Anderson Cancer Center