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Article: Serum and glucocorticoid kinase 3 at 8q13.1 promotes cell proliferation and survival in hepatocellular carcinoma
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TitleSerum and glucocorticoid kinase 3 at 8q13.1 promotes cell proliferation and survival in hepatocellular carcinoma
 
AuthorsLiu, M2
Chen, L2
Chan, THM2
Wang, J2
Li, Y
Li, Y
Zeng, TT1
Yuan, YF1
Guan, XY2 1
 
Issue Date2012
 
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/
 
CitationHepatology, 2012, v. 55 n. 6, p. 1754-1765 [How to Cite?]
DOI: http://dx.doi.org/10.1002/hep.25584
 
AbstractAmplification of broad regions of 8q is one of the most frequent genetic alterations in hepatocellular carcinoma (HCC), suggesting the existence of oncogenes in addition to MYC at 8q24.21. In this report we examine the potential role of the candidate amplified oncogene serum and glucocorticoid kinase 3 (SGK3) at 8q13.1 in HCC pathogenesis. We found amplification and overexpression of SGK3 was frequently detected in clinical HCC specimens and that SGK3 genomic activation was significantly associated with poor outcome of patients (P = 0.028). Functionally, we found that overexpression of SGK3 in HCC cells increased cell cycle progression through G 1, cell survival, clonogenicity, anchorage-independent growth, and tumor formation in nude mice. In contrast, RNA interference (RNAi) silencing of SGK3 inhibited its oncogenic effects. We provide evidence that SGK3 promotes HCC growth and survival through inactivating glycogen synthase kinase 3 beta and Bcl-2-associated death promoter, respectively. We also found that expression of SGK3, which like AKT is activated by PI3K/PDK1 signaling, has more significance than overexpression of AKT in predicting poor outcome in HCC patients. Taken together, our findings in the present study suggests that the SGK3 pathway may function in parallel with the AKT pathway and undergoes an AKT-independent signaling pathway in the pathogenesis of HCC. Further characterization of SGK3 may provide a prognostic biomarker for HCC outcome prediction and a novel therapeutic target in HCC treatment. © 2012 American Association for the Study of Liver Diseases.
 
ISSN0270-9139
2013 Impact Factor: 11.190
 
DOIhttp://dx.doi.org/10.1002/hep.25584
 
ISI Accession Number IDWOS:000304530200014
Funding AgencyGrant Number
Hong Kong Research Grant CouncilHKU5/CRF/08
HKBU5/CRF/10
HKU7/CRF/09
Sun Yat-Sen University85000-3171311
Funding Information:

Supported by Hong Kong Research Grant Council Collaborative Research Funds (HKU5/CRF/08, HKBU5/CRF/10 and HKU7/CRF/09) and the "Hundred Talents Program" at Sun Yat-Sen University (85000-3171311).

 
GrantsMass spectrometry-based metabolomics for the characterization of cellular metabolic pathways associated with the development of hepatocellular carcinoma
Liver Transplantation Research Centre: A Multidisciplinary Study for Liver Graft Injury
 
DC FieldValue
dc.contributor.authorLiu, M
 
dc.contributor.authorChen, L
 
dc.contributor.authorChan, THM
 
dc.contributor.authorWang, J
 
dc.contributor.authorLi, Y
 
dc.contributor.authorLi, Y
 
dc.contributor.authorZeng, TT
 
dc.contributor.authorYuan, YF
 
dc.contributor.authorGuan, XY
 
dc.date.accessioned2012-06-26T06:12:41Z
 
dc.date.available2012-06-26T06:12:41Z
 
dc.date.issued2012
 
dc.description.abstractAmplification of broad regions of 8q is one of the most frequent genetic alterations in hepatocellular carcinoma (HCC), suggesting the existence of oncogenes in addition to MYC at 8q24.21. In this report we examine the potential role of the candidate amplified oncogene serum and glucocorticoid kinase 3 (SGK3) at 8q13.1 in HCC pathogenesis. We found amplification and overexpression of SGK3 was frequently detected in clinical HCC specimens and that SGK3 genomic activation was significantly associated with poor outcome of patients (P = 0.028). Functionally, we found that overexpression of SGK3 in HCC cells increased cell cycle progression through G 1, cell survival, clonogenicity, anchorage-independent growth, and tumor formation in nude mice. In contrast, RNA interference (RNAi) silencing of SGK3 inhibited its oncogenic effects. We provide evidence that SGK3 promotes HCC growth and survival through inactivating glycogen synthase kinase 3 beta and Bcl-2-associated death promoter, respectively. We also found that expression of SGK3, which like AKT is activated by PI3K/PDK1 signaling, has more significance than overexpression of AKT in predicting poor outcome in HCC patients. Taken together, our findings in the present study suggests that the SGK3 pathway may function in parallel with the AKT pathway and undergoes an AKT-independent signaling pathway in the pathogenesis of HCC. Further characterization of SGK3 may provide a prognostic biomarker for HCC outcome prediction and a novel therapeutic target in HCC treatment. © 2012 American Association for the Study of Liver Diseases.
 
dc.description.natureLink_to_OA_fulltext
 
dc.identifier.citationHepatology, 2012, v. 55 n. 6, p. 1754-1765 [How to Cite?]
DOI: http://dx.doi.org/10.1002/hep.25584
 
dc.identifier.doihttp://dx.doi.org/10.1002/hep.25584
 
dc.identifier.eissn1527-3350
 
dc.identifier.epage1765
 
dc.identifier.hkuros203489
 
dc.identifier.hkuros232349
 
dc.identifier.isiWOS:000304530200014
Funding AgencyGrant Number
Hong Kong Research Grant CouncilHKU5/CRF/08
HKBU5/CRF/10
HKU7/CRF/09
Sun Yat-Sen University85000-3171311
Funding Information:

Supported by Hong Kong Research Grant Council Collaborative Research Funds (HKU5/CRF/08, HKBU5/CRF/10 and HKU7/CRF/09) and the "Hundred Talents Program" at Sun Yat-Sen University (85000-3171311).

 
dc.identifier.issn0270-9139
2013 Impact Factor: 11.190
 
dc.identifier.issue6
 
dc.identifier.pmid22262416
 
dc.identifier.scopuseid_2-s2.0-84861574782
 
dc.identifier.spage1754
 
dc.identifier.urihttp://hdl.handle.net/10722/150855
 
dc.identifier.volume55
 
dc.languageeng
 
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofHepatology
 
dc.relation.projectMass spectrometry-based metabolomics for the characterization of cellular metabolic pathways associated with the development of hepatocellular carcinoma
 
dc.relation.projectLiver Transplantation Research Centre: A Multidisciplinary Study for Liver Graft Injury
 
dc.subject.meshCarcinoma, Hepatocellular - enzymology - pathology
 
dc.subject.meshChromosomes, Human, Pair 8
 
dc.subject.meshGlycogen Synthase Kinase 3 - physiology
 
dc.subject.meshLiver Neoplasms - enzymology - pathology
 
dc.subject.meshProtein-Serine-Threonine Kinases - genetics - physiology
 
dc.titleSerum and glucocorticoid kinase 3 at 8q13.1 promotes cell proliferation and survival in hepatocellular carcinoma
 
dc.typeArticle
 
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<contributor.author>Chan, THM</contributor.author>
<contributor.author>Wang, J</contributor.author>
<contributor.author>Li, Y</contributor.author>
<contributor.author>Li, Y</contributor.author>
<contributor.author>Zeng, TT</contributor.author>
<contributor.author>Yuan, YF</contributor.author>
<contributor.author>Guan, XY</contributor.author>
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<description.abstract>Amplification of broad regions of 8q is one of the most frequent genetic alterations in hepatocellular carcinoma (HCC), suggesting the existence of oncogenes in addition to MYC at 8q24.21. In this report we examine the potential role of the candidate amplified oncogene serum and glucocorticoid kinase 3 (SGK3) at 8q13.1 in HCC pathogenesis. We found amplification and overexpression of SGK3 was frequently detected in clinical HCC specimens and that SGK3 genomic activation was significantly associated with poor outcome of patients (P = 0.028). Functionally, we found that overexpression of SGK3 in HCC cells increased cell cycle progression through G 1, cell survival, clonogenicity, anchorage-independent growth, and tumor formation in nude mice. In contrast, RNA interference (RNAi) silencing of SGK3 inhibited its oncogenic effects. We provide evidence that SGK3 promotes HCC growth and survival through inactivating glycogen synthase kinase 3 beta and Bcl-2-associated death promoter, respectively. We also found that expression of SGK3, which like AKT is activated by PI3K/PDK1 signaling, has more significance than overexpression of AKT in predicting poor outcome in HCC patients. Taken together, our findings in the present study suggests that the SGK3 pathway may function in parallel with the AKT pathway and undergoes an AKT-independent signaling pathway in the pathogenesis of HCC. Further characterization of SGK3 may provide a prognostic biomarker for HCC outcome prediction and a novel therapeutic target in HCC treatment. &#169; 2012 American Association for the Study of Liver Diseases.</description.abstract>
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Author Affiliations
  1. Sun Yat-Sen University Cancer Center
  2. The University of Hong Kong