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Article: Sox9 confers stemness properties in hepatocellular carcinoma through Frizzled-7 mediated Wnt/β-catenin signaling

TitleSox9 confers stemness properties in hepatocellular carcinoma through Frizzled-7 mediated Wnt/β-catenin signaling
Authors
KeywordsSox9
Liver cancer
Tumor-initiating cells
Issue Date2016
PublisherImpact Journals LLC. The Journal's web site is located at http://www.impactjournals.com/oncotarget/index.html
Citation
Oncotarget, 2016, v. 7 n. 20, p. 29371-29386 How to Cite?
AbstractSox9, an SRY-related HMG box transcription factor, is a progenitor/precursor cell marker of the liver expressed during embryogenesis and following liver injury. In this study, we investigated the role of Sox9 and its molecular mechanism with reference to stemness properties in hepatocellular carcinoma (HCC). Here, we observed upregulation of Sox9 in human HCC tissues compared with the non-tumorous liver counterparts (p < 0.001). Upregulation of Sox9 transcript level was associated with poorer tumor cell differentiation (p = 0.003), venous invasion (p = 0.026), advanced tumor stage (p = 0.044) and shorter overall survival (p = 0.042). Transcript levels of Sox9 and CD24 were positively correlated. Silencing of Sox9 in HCC cells inhibited in vitro cell proliferation and tumorsphere formation, sensitized HCC cells to chemotherapeutic agents, and suppressed in vivo tumorigenicity. In addition, knockdown of Sox9 suppressed HCC cell migration, invasion, and in vivo lung metastasis. Further studies showed that Sox9 endowed stemness features through activation of Wnt/β-catenin signaling, which was confirmed by the partial rescue effect on tumorigenicity and self-renewal upon transfection of active β-catenin in Sox9 knockdown cells. By ChIP and luciferase promoter assays, Frizzled-7 was identified to be the direct transcriptional target of Sox9. In conclusion, Sox9 confers stemness properties of HCC through Frizzled-7 mediated Wnt/β-catenin pathway.
Persistent Identifierhttp://hdl.handle.net/10722/225637
ISSN
2015 Impact Factor: 5.008
2015 SCImago Journal Rankings: 2.294
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLeung, CON-
dc.contributor.authorMak, WN-
dc.contributor.authorKai, AKL-
dc.contributor.authorChan, KS-
dc.contributor.authorLee, TKW-
dc.contributor.authorNg, IOL-
dc.contributor.authorLo, RCL-
dc.date.accessioned2016-05-20T08:09:39Z-
dc.date.available2016-05-20T08:09:39Z-
dc.date.issued2016-
dc.identifier.citationOncotarget, 2016, v. 7 n. 20, p. 29371-29386-
dc.identifier.issn1949-2553-
dc.identifier.urihttp://hdl.handle.net/10722/225637-
dc.description.abstractSox9, an SRY-related HMG box transcription factor, is a progenitor/precursor cell marker of the liver expressed during embryogenesis and following liver injury. In this study, we investigated the role of Sox9 and its molecular mechanism with reference to stemness properties in hepatocellular carcinoma (HCC). Here, we observed upregulation of Sox9 in human HCC tissues compared with the non-tumorous liver counterparts (p < 0.001). Upregulation of Sox9 transcript level was associated with poorer tumor cell differentiation (p = 0.003), venous invasion (p = 0.026), advanced tumor stage (p = 0.044) and shorter overall survival (p = 0.042). Transcript levels of Sox9 and CD24 were positively correlated. Silencing of Sox9 in HCC cells inhibited in vitro cell proliferation and tumorsphere formation, sensitized HCC cells to chemotherapeutic agents, and suppressed in vivo tumorigenicity. In addition, knockdown of Sox9 suppressed HCC cell migration, invasion, and in vivo lung metastasis. Further studies showed that Sox9 endowed stemness features through activation of Wnt/β-catenin signaling, which was confirmed by the partial rescue effect on tumorigenicity and self-renewal upon transfection of active β-catenin in Sox9 knockdown cells. By ChIP and luciferase promoter assays, Frizzled-7 was identified to be the direct transcriptional target of Sox9. In conclusion, Sox9 confers stemness properties of HCC through Frizzled-7 mediated Wnt/β-catenin pathway.-
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.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectSox9-
dc.subjectLiver cancer-
dc.subjectTumor-initiating cells-
dc.titleSox9 confers stemness properties in hepatocellular carcinoma through Frizzled-7 mediated Wnt/β-catenin signaling-
dc.typeArticle-
dc.identifier.emailLeung, CON: conleung@hku.hk-
dc.identifier.emailMak, WN: wnmak@connect.hku.hk-
dc.identifier.emailKai, AKL: klakai@hku.hk-
dc.identifier.emailLee, TKW: tkwlee@HKUCC-COM.hku.hk-
dc.identifier.emailNg, IOL: iolng@hku.hk-
dc.identifier.emailLo, RCL: loregina@hku.hk-
dc.identifier.authorityLee, TKW=rp00447-
dc.identifier.authorityNg, IOL=rp00335-
dc.identifier.authorityLo, RCL=rp01359-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.18632/oncotarget.8835-
dc.identifier.pmid27105493-
dc.identifier.pmcidPMC5045402-
dc.identifier.scopuseid_2-s2.0-84969800124-
dc.identifier.hkuros257983-
dc.identifier.volume7-
dc.identifier.issue20-
dc.identifier.spage29371-
dc.identifier.epage29386-
dc.identifier.isiWOS:000377742600049-
dc.publisher.placeUnited States-
dc.identifier.issnl1949-2553-

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