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Article: Proline-rich tyrosine kinase 2 (Pyk2) promotes proliferation and invasiveness of hepatocellular carcinoma cells through c-Src/ERK activation

TitleProline-rich tyrosine kinase 2 (Pyk2) promotes proliferation and invasiveness of hepatocellular carcinoma cells through c-Src/ERK activation
Authors
Issue Date2008
PublisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
Citation
Carcinogenesis, 2008, v. 29 n. 11, p. 2096-2105 How to Cite?
AbstractThe aim of the current study is to elucidate the mechanism of proline-rich tyrosine kinase 2 (Pyk2)-mediated cell proliferation and invasiveness in hepatocellular carcinoma (HCC) cells. Human HCC cell lines PLC and MHCC97L were stably transfected with either full-length Pyk2 or C-terminal non-kinase region of Pyk2 (PRNK). Functional studies on cell proliferation and invasion were conducted in vitro by colony formation assay, adhesion assay, migration assay and wound-healing assay. For the in vivo study, an orthotopic nude mice liver tumor model was applied to investigate the effects of Pyk2 overexpression on tumor growth and metastasis. Overexpression of Pyk2 in PLC cells resulted in an upregulation of colony formation (P = 0.021) and adhesion toward laminin (P = 0.018). Pyk2 promoted wound recovery by stimulation of actin stress fiber polymerization. In the in vivo study, transfection of PRNK in MHCC97L cells significantly decreased tumor volume (P = 0.001) and the incidence of lung metastasis (P = 0.014). Overexpression of Pyk2 promoted the activation of c-Src, formation of Pyk2/c-Src complex and activated the extracellular signal-regulated kinase (ERK)/ mitogen-activated protein kinase (MAPK)-signaling pathway. Pyk2 upregulated the activation of ERK1/2 that is insensitive to MAPK/ERK kinase (MEK)1/2 inhibition. On the contrary, PRNK overexpression downregulated the activation of c-Src and ERK/MAPK-signaling pathways. Immunofluorescence staining showed that the focal adhesion localization of Pyk2 is a major determinant for c-Src and ERK/MAPK activation. In conclusion, our results showed that Pyk2 promoted cell proliferation and invasiveness by upregulation of the c-Src and ERK/MAPK-signaling pathways. © The Author 2008. Published by Oxford University Press. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/59912
ISSN
2015 Impact Factor: 4.874
2015 SCImago Journal Rankings: 2.439
ISI Accession Number ID
Funding AgencyGrant Number
Council General Research Funding757406
Funding Information:

Research Grant Council General Research Funding (757406), Hong Kong.

References

 

DC FieldValueLanguage
dc.contributor.authorSun, CKen_HK
dc.contributor.authorMan, Ken_HK
dc.contributor.authorNg, KTen_HK
dc.contributor.authorHo, JWen_HK
dc.contributor.authorLim, ZXen_HK
dc.contributor.authorCheng, Qen_HK
dc.contributor.authorLo, CMen_HK
dc.contributor.authorPoon, RTen_HK
dc.contributor.authorFan, STen_HK
dc.date.accessioned2010-05-31T03:59:58Z-
dc.date.available2010-05-31T03:59:58Z-
dc.date.issued2008en_HK
dc.identifier.citationCarcinogenesis, 2008, v. 29 n. 11, p. 2096-2105en_HK
dc.identifier.issn0143-3334en_HK
dc.identifier.urihttp://hdl.handle.net/10722/59912-
dc.description.abstractThe aim of the current study is to elucidate the mechanism of proline-rich tyrosine kinase 2 (Pyk2)-mediated cell proliferation and invasiveness in hepatocellular carcinoma (HCC) cells. Human HCC cell lines PLC and MHCC97L were stably transfected with either full-length Pyk2 or C-terminal non-kinase region of Pyk2 (PRNK). Functional studies on cell proliferation and invasion were conducted in vitro by colony formation assay, adhesion assay, migration assay and wound-healing assay. For the in vivo study, an orthotopic nude mice liver tumor model was applied to investigate the effects of Pyk2 overexpression on tumor growth and metastasis. Overexpression of Pyk2 in PLC cells resulted in an upregulation of colony formation (P = 0.021) and adhesion toward laminin (P = 0.018). Pyk2 promoted wound recovery by stimulation of actin stress fiber polymerization. In the in vivo study, transfection of PRNK in MHCC97L cells significantly decreased tumor volume (P = 0.001) and the incidence of lung metastasis (P = 0.014). Overexpression of Pyk2 promoted the activation of c-Src, formation of Pyk2/c-Src complex and activated the extracellular signal-regulated kinase (ERK)/ mitogen-activated protein kinase (MAPK)-signaling pathway. Pyk2 upregulated the activation of ERK1/2 that is insensitive to MAPK/ERK kinase (MEK)1/2 inhibition. On the contrary, PRNK overexpression downregulated the activation of c-Src and ERK/MAPK-signaling pathways. Immunofluorescence staining showed that the focal adhesion localization of Pyk2 is a major determinant for c-Src and ERK/MAPK activation. In conclusion, our results showed that Pyk2 promoted cell proliferation and invasiveness by upregulation of the c-Src and ERK/MAPK-signaling pathways. © The Author 2008. Published by Oxford University Press. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/en_HK
dc.relation.ispartofCarcinogenesisen_HK
dc.subject.meshCarcinoma, Hepatocellular - enzymology - pathology-
dc.subject.meshCell Proliferation-
dc.subject.meshExtracellular Signal-Regulated MAP Kinases - metabolism-
dc.subject.meshFocal Adhesion Kinase 2 - metabolism-
dc.subject.meshLiver Neoplasms - enzymology - pathology-
dc.titleProline-rich tyrosine kinase 2 (Pyk2) promotes proliferation and invasiveness of hepatocellular carcinoma cells through c-Src/ERK activationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0143-3334&volume=29&issue=11&spage=2096&epage=2105&date=2008&atitle=Proline-rich+tyrosine+kinase+2+(Pyk2)+promotes+proliferation+and+invasiveness+of+hepatocellular+carcinoma+cells+through+c-Src/ERK+activationen_HK
dc.identifier.emailMan, K: kwanman@hku.hken_HK
dc.identifier.emailNg, KT: ledodes@hku.hken_HK
dc.identifier.emailLo, CM: chungmlo@hkucc.hku.hken_HK
dc.identifier.emailPoon, RT: poontp@hku.hken_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.authorityMan, K=rp00417en_HK
dc.identifier.authorityNg, KT=rp01720en_HK
dc.identifier.authorityLo, CM=rp00412en_HK
dc.identifier.authorityPoon, RT=rp00446en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1093/carcin/bgn203en_HK
dc.identifier.pmid18765415-
dc.identifier.scopuseid_2-s2.0-56049123161en_HK
dc.identifier.hkuros153747en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-56049123161&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume29en_HK
dc.identifier.issue11en_HK
dc.identifier.spage2096en_HK
dc.identifier.epage2105en_HK
dc.identifier.isiWOS:000260977900007-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridSun, CK=7404248685en_HK
dc.identifier.scopusauthoridMan, K=7101754072en_HK
dc.identifier.scopusauthoridNg, KT=7403178513en_HK
dc.identifier.scopusauthoridHo, JW=7402649982en_HK
dc.identifier.scopusauthoridLim, ZX=25822628500en_HK
dc.identifier.scopusauthoridCheng, Q=16024087700en_HK
dc.identifier.scopusauthoridLo, CM=7401771672en_HK
dc.identifier.scopusauthoridPoon, RT=7103097223en_HK
dc.identifier.scopusauthoridFan, ST=7402678224en_HK

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