File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Deleted in liver cancer 2 suppresses cell growth via the regulation of the Raf-1-ERK1/2-p70S6K signalling pathway

TitleDeleted in liver cancer 2 suppresses cell growth via the regulation of the Raf-1-ERK1/2-p70S6K signalling pathway
Authors
KeywordsCell growth suppression
DLC2 (deleted in liver cancer 2)
Hepatocellular carcinoma
Raf-1-ERK1/2-p70S6K signalling
Issue Date2010
PublisherWiley-Blackwell Publishing, Inc.. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=1478-3223&site=1
Citation
Liver International, 2010, v. 30 n. 9, p. 1315-1323 How to Cite?
AbstractBackground: Deleted in liver cancer 2 (DLC2) gene, a putative tumour suppressor gene, encodes a Rho GTPase-activating protein (RhoGAP) with GAP activity specific for RhoA. It exhibits tumour suppressor functions and inhibits tumour cell proliferation, migration as well as transformation. Aims: In this study, we aimed to investigate the underlying mechanisms of the DLC2 gene in suppressing cell migration and cell growth. HepG2 hepatoma cells were stably transfected with the DLC2γ isoform, which contains the RhoGAP domain. Methods and results: On performing immunofluorescence staining and Western blot analysis, the expression of the focal adhesion protein paxillin was found to be much reduced in DLC2γ-stable clones. Upon flow cytometric analysis of the cell cycle profiles, the DLC2γ-stable clones were shown to have a higher population of cells arrested at the G1 phase than the EGFP vector-stable clone, suggesting that downregulation of RhoA activity in DLC2γ-stable clones inhibited cell cycle progression. In the DLC2γ-stable clone, the levels of Raf-1 and extracellular signal-regulated kinase (ERK) 1/2 were decreased as compared with those of the parental HepG2, EGFP vector and DLC2γ-GAP defective mutant-stable clones. Furthermore, the ribosomal kinase p70S6K, a downstream target of ERK1/2, was suppressed in the DLC2-stable clones. On the contrary, when DLC2 was knocked down by siRNA in HepG2 cells, the expression levels of phospho-p70S6K and phospho-ERK1/2 were upregulated. Conclusion: Our data show that DLC2 inhibits the activity of Raf-1-ERK1/2-p70S6K via its RhoGAP function, resulting in the suppression of cell growth. Further studies on the molecular signalling between DLC2 and p70S6K may provide an insight into its growth suppressor function. © 2010 John Wiley & Sons A/S.
Persistent Identifierhttp://hdl.handle.net/10722/123998
ISSN
2015 Impact Factor: 4.47
2015 SCImago Journal Rankings: 1.677
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grants Council (RGC)HKU 1/06C
7/CRF/09
Funding Information:

This study was funded by Hong Kong Research Grants Council (RGC) Collaborative Research Fund (HKU 1/06C and 7/CRF/09). IOL Ng is Loke Yew Professor in Pathology.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorLeung, THYen_HK
dc.contributor.authorYam, JWPen_HK
dc.contributor.authorChan, LKen_HK
dc.contributor.authorChing, YPen_HK
dc.contributor.authorNg, IOLen_HK
dc.date.accessioned2010-10-18T08:41:26Z-
dc.date.available2010-10-18T08:41:26Z-
dc.date.issued2010en_HK
dc.identifier.citationLiver International, 2010, v. 30 n. 9, p. 1315-1323en_HK
dc.identifier.issn1478-3223en_HK
dc.identifier.urihttp://hdl.handle.net/10722/123998-
dc.description.abstractBackground: Deleted in liver cancer 2 (DLC2) gene, a putative tumour suppressor gene, encodes a Rho GTPase-activating protein (RhoGAP) with GAP activity specific for RhoA. It exhibits tumour suppressor functions and inhibits tumour cell proliferation, migration as well as transformation. Aims: In this study, we aimed to investigate the underlying mechanisms of the DLC2 gene in suppressing cell migration and cell growth. HepG2 hepatoma cells were stably transfected with the DLC2γ isoform, which contains the RhoGAP domain. Methods and results: On performing immunofluorescence staining and Western blot analysis, the expression of the focal adhesion protein paxillin was found to be much reduced in DLC2γ-stable clones. Upon flow cytometric analysis of the cell cycle profiles, the DLC2γ-stable clones were shown to have a higher population of cells arrested at the G1 phase than the EGFP vector-stable clone, suggesting that downregulation of RhoA activity in DLC2γ-stable clones inhibited cell cycle progression. In the DLC2γ-stable clone, the levels of Raf-1 and extracellular signal-regulated kinase (ERK) 1/2 were decreased as compared with those of the parental HepG2, EGFP vector and DLC2γ-GAP defective mutant-stable clones. Furthermore, the ribosomal kinase p70S6K, a downstream target of ERK1/2, was suppressed in the DLC2-stable clones. On the contrary, when DLC2 was knocked down by siRNA in HepG2 cells, the expression levels of phospho-p70S6K and phospho-ERK1/2 were upregulated. Conclusion: Our data show that DLC2 inhibits the activity of Raf-1-ERK1/2-p70S6K via its RhoGAP function, resulting in the suppression of cell growth. Further studies on the molecular signalling between DLC2 and p70S6K may provide an insight into its growth suppressor function. © 2010 John Wiley & Sons A/S.en_HK
dc.languageeng-
dc.publisherWiley-Blackwell Publishing, Inc.. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=1478-3223&site=1en_HK
dc.relation.ispartofLiver Internationalen_HK
dc.rightsThe definitive version is available at www.blackwell-synergy.com-
dc.subjectCell growth suppressionen_HK
dc.subjectDLC2 (deleted in liver cancer 2)en_HK
dc.subjectHepatocellular carcinomaen_HK
dc.subjectRaf-1-ERK1/2-p70S6K signallingen_HK
dc.titleDeleted in liver cancer 2 suppresses cell growth via the regulation of the Raf-1-ERK1/2-p70S6K signalling pathwayen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1478-3223&volume=30&issue=9&spage=1315&epage=1323&date=2010&atitle=Deleted+in+liver+cancer+2+suppresses+cell+growth+via+regulation+of+the+Raf-1-ERK1/2-p70S6K+signalling+pathway-
dc.identifier.emailYam, JWP:judyyam@pathology.hku.hken_HK
dc.identifier.emailChing, YP:ypching@hku.hken_HK
dc.identifier.emailNg, IOL:iolng@hkucc.hku.hken_HK
dc.identifier.authorityYam, JWP=rp00468en_HK
dc.identifier.authorityChing, YP=rp00469en_HK
dc.identifier.authorityNg, IOL=rp00335en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1111/j.1478-3231.2010.02307.xen_HK
dc.identifier.pmid20629949-
dc.identifier.scopuseid_2-s2.0-78349241737en_HK
dc.identifier.hkuros172119-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78349241737&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume30en_HK
dc.identifier.issue9en_HK
dc.identifier.spage1315en_HK
dc.identifier.epage1323en_HK
dc.identifier.isiWOS:000281551200008-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectMolecular pathology of liver cancer - a multidisciplinary study-
dc.identifier.scopusauthoridLeung, THY=7202110922en_HK
dc.identifier.scopusauthoridYam, JWP=6603711123en_HK
dc.identifier.scopusauthoridChan, LK=24833005000en_HK
dc.identifier.scopusauthoridChing, YP=7005431277en_HK
dc.identifier.scopusauthoridNg, IOL=7102753722en_HK
dc.identifier.citeulike7862338-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats