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Article: Serum and glucocorticoid kinase 3 at 8q13.1 promotes cell proliferation and survival in hepatocellular carcinoma

TitleSerum and glucocorticoid kinase 3 at 8q13.1 promotes cell proliferation and survival in hepatocellular carcinoma
Authors
Issue Date2012
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/
Citation
Hepatology, 2012, v. 55 n. 6, p. 1754-1765 How to Cite?
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. © 2012 American Association for the Study of Liver Diseases.
Persistent Identifierhttp://hdl.handle.net/10722/150855
ISSN
2013 Impact Factor: 11.190
ISI Accession Number ID
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).

Grants

 

Author Affiliations
  1. Sun Yat-Sen University Cancer Center
  2. The University of Hong Kong
DC FieldValueLanguage
dc.contributor.authorLiu, Men_US
dc.contributor.authorChen, Len_US
dc.contributor.authorChan, THMen_US
dc.contributor.authorWang, Jen_US
dc.contributor.authorLi, Yen_US
dc.contributor.authorLi, Yen_US
dc.contributor.authorZeng, TTen_US
dc.contributor.authorYuan, YFen_US
dc.contributor.authorGuan, XYen_US
dc.date.accessioned2012-06-26T06:12:41Z-
dc.date.available2012-06-26T06:12:41Z-
dc.date.issued2012en_US
dc.identifier.citationHepatology, 2012, v. 55 n. 6, p. 1754-1765en_US
dc.identifier.issn0270-9139en_US
dc.identifier.urihttp://hdl.handle.net/10722/150855-
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.en_US
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/en_US
dc.relation.ispartofHepatologyen_US
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 carcinomaen_US
dc.typeArticleen_US
dc.identifier.emailGuan, XY:xyguan@hkucc.hku.hken_US
dc.identifier.authorityGuan, XY=rp00454en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1002/hep.25584en_US
dc.identifier.pmid22262416-
dc.identifier.scopuseid_2-s2.0-84861574782-
dc.identifier.hkuros203489-
dc.identifier.hkuros232349-
dc.identifier.volume55-
dc.identifier.issue6-
dc.identifier.spage1754-
dc.identifier.epage1765-
dc.identifier.eissn1527-3350-
dc.identifier.isiWOS:000304530200014-
dc.publisher.placeUnited Statesen_US
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.identifier.scopusauthoridLiu, M=23489325900en_US
dc.identifier.scopusauthoridChen, L=23569135400en_US
dc.identifier.scopusauthoridChan, THM=26431726400en_US
dc.identifier.scopusauthoridWang, J=55192755600en_US
dc.identifier.scopusauthoridLi, Y=54970821900en_US
dc.identifier.scopusauthoridLi, Y=53980173200en_US
dc.identifier.scopusauthoridZeng, TT=55192299800en_US
dc.identifier.scopusauthoridYuan, YF=55192680800en_US
dc.identifier.scopusauthoridGuan, XY=7201463221en_US

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