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Article: Integrin-linked kinase overexpression and its oncogenic role in promoting tumorigenicity of hepatocellular carcinoma

TitleIntegrin-linked kinase overexpression and its oncogenic role in promoting tumorigenicity of hepatocellular carcinoma
Authors
KeywordsCancer inhibition
Enzyme phosphorylation
Liver carcinogenesis
Integrin linked kinase
Protein function
Issue Date2011
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2011, v. 6 n. 2 How to Cite?
AbstractBackground: Integrin-linked kinase (ILK) was first discovered as an integrin β1-subunit binding protein. It localizes at the focal adhesions and is involved in cytoskeleton remodeling. ILK overexpression and its dysregulated signaling cascades have been reported in many human cancers. Aberrant expression of ILK influenced a wide range of signaling pathways and cellular functions. Although ILK has been well characterized in many malignancies, its role in hepatocellular carcinoma (HCC) is still largely unknown. Methodology/Principal Findings: Quantitative PCR analysis was used to examine ILK mRNA expression in HCC clinical samples. It was shown that ILK was overexpressed in 36.9% (21/57) of HCC tissues when compared to the corresponding non-tumorous livers. The overall ILK expression level was significantly higher in tumorous tissues (P = 0.004), with a significant stepwise increase in expression level along tumor progression from tumor stage I to IV (P = 0.045). ILK knockdown stable clones were established in two HCC cell lines, BEL7402 and HLE, and were subjected to different functional assays. Knockdown of ILK significantly suppressed HCC cell growth, motility and invasion in vitro and inhibited tumorigenicity in vivo. Western blot analysis revealed a reduced phosphorylated-Akt (pAkt) at Serine-473 expression in ILK knockdown stable clones when compared to control clones. Conclusion/Significance: This study provides evidence about the clinical relevance of ILK in hepatocarcinogenesis. ILK was found to be progressively elevated along HCC progression. Here our findings also provide the first validation about the oncogenic capacity of ILK in vivo by suppressing its expression in HCC cells. The oncogenic role of ILK is implicated to be mediated by Akt pathway. © 2011 Chan et al.
Persistent Identifierhttp://hdl.handle.net/10722/135690
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
University of Hong Kong
Hong Kong Research Grants CouncilHKU7798/07M
Outstanding Young Researcher Award
Funding Information:

This work was supported by The University of Hong Kong Seed Funding Programme for Basic Research, Hong Kong Research Grants Council (HKU7798/07M), and Outstanding Young Researcher Award (to J.W.P. Yam). I.O.L. Ng is Loke Yew Professor in Pathology. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

 

DC FieldValueLanguage
dc.contributor.authorChan, Jen_HK
dc.contributor.authorKo, FCFen_HK
dc.contributor.authorYeung, YSen_HK
dc.contributor.authorNg, IOLen_HK
dc.contributor.authorYam, JWPen_HK
dc.date.accessioned2011-07-27T01:39:32Z-
dc.date.available2011-07-27T01:39:32Z-
dc.date.issued2011en_HK
dc.identifier.citationPlos One, 2011, v. 6 n. 2en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/135690-
dc.description.abstractBackground: Integrin-linked kinase (ILK) was first discovered as an integrin β1-subunit binding protein. It localizes at the focal adhesions and is involved in cytoskeleton remodeling. ILK overexpression and its dysregulated signaling cascades have been reported in many human cancers. Aberrant expression of ILK influenced a wide range of signaling pathways and cellular functions. Although ILK has been well characterized in many malignancies, its role in hepatocellular carcinoma (HCC) is still largely unknown. Methodology/Principal Findings: Quantitative PCR analysis was used to examine ILK mRNA expression in HCC clinical samples. It was shown that ILK was overexpressed in 36.9% (21/57) of HCC tissues when compared to the corresponding non-tumorous livers. The overall ILK expression level was significantly higher in tumorous tissues (P = 0.004), with a significant stepwise increase in expression level along tumor progression from tumor stage I to IV (P = 0.045). ILK knockdown stable clones were established in two HCC cell lines, BEL7402 and HLE, and were subjected to different functional assays. Knockdown of ILK significantly suppressed HCC cell growth, motility and invasion in vitro and inhibited tumorigenicity in vivo. Western blot analysis revealed a reduced phosphorylated-Akt (pAkt) at Serine-473 expression in ILK knockdown stable clones when compared to control clones. Conclusion/Significance: This study provides evidence about the clinical relevance of ILK in hepatocarcinogenesis. ILK was found to be progressively elevated along HCC progression. Here our findings also provide the first validation about the oncogenic capacity of ILK in vivo by suppressing its expression in HCC cells. The oncogenic role of ILK is implicated to be mediated by Akt pathway. © 2011 Chan et al.en_HK
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_HK
dc.relation.ispartofPLoS ONEen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectCancer inhibition-
dc.subjectEnzyme phosphorylation-
dc.subjectLiver carcinogenesis-
dc.subjectIntegrin linked kinase-
dc.subjectProtein function-
dc.titleIntegrin-linked kinase overexpression and its oncogenic role in promoting tumorigenicity of hepatocellular carcinomaen_HK
dc.typeArticleen_HK
dc.identifier.emailNg, IOL:iolng@hkucc.hku.hken_HK
dc.identifier.emailYam, JWP:judyyam@pathology.hku.hken_HK
dc.identifier.authorityNg, IOL=rp00335en_HK
dc.identifier.authorityYam, JWP=rp00468en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0016984en_HK
dc.identifier.pmid21347395-
dc.identifier.pmcidPMC3036736-
dc.identifier.scopuseid_2-s2.0-79951803441en_HK
dc.identifier.hkuros187411en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79951803441&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume6en_HK
dc.identifier.issue2en_HK
dc.identifier.spagee16984en_US
dc.identifier.epagee16984en_US
dc.identifier.eissn1932-6203-
dc.identifier.isiWOS:000287361700061-
dc.publisher.placeUnited Statesen_HK

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