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Article: Proline-rich tyrosine kinase 2 (Pyk2) promotes cell motility of hepatocellular carcinoma through induction of epithelial to mesenchymal transition

TitleProline-rich tyrosine kinase 2 (Pyk2) promotes cell motility of hepatocellular carcinoma through induction of epithelial to mesenchymal transition
Authors
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. 4 How to Cite?
AbstractAims: Proline-rich tyrosine kinase 2 (Pyk2), a non-receptor tyrosine kinase of the focal adhesion kinase (FAK) family, is up-regulated in more than 60% of the tumors of hepatocellular carcinoma (HCC) patients. Forced overexpression of Pyk2 can promote the proliferation and invasion of HCC cells. In this study, we aimed to explore the underlying molecular mechanism of Pyk2-mediated cell migration of HCC cells. Methodology/Principal Findings: We demonstrated that Pyk2 transformed the epithelial HCC cell line Hep3B into a mesenchymal phenotype via the induction of epithelial to mesenchymal transition (EMT), signified by the up-regulation of membrane ruffle formation, activation of Rac/Rho GTPases, down-regulation of epithelial genes E-cadherin and cytokeratin as well as promotion of cell motility in presence of lysophosphatidic acid (LPA). Suppression of Pyk2 by overexpression of dominant negative PRNK domain in the metastatic HCC cell line MHCC97L transformed its fibroblastoid phenotype to an epithelial phenotype with up-regulation of epithelial genes, down-regulation of mesenchymal genes N-cadherin and STAT5b, and reduction of LPA-induced membrane ruffle formation and cell motility. Moreover, overexpression of Pyk2 in Hep3B cells promoted the phosphorylation and localization of mesenchymal gene Hic-5 onto cell membrane while suppression of Pyk2 in MHCC97L cells attenuated its phosphorylation and localization. Conclusion: These data provided new evidence of the underlying mechanism of Pyk2 in controlling cell motility of HCC cells through regulation of genes associated with EMT. © 2011 Sun et al.
Persistent Identifierhttp://hdl.handle.net/10722/135527
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Research Grant Council Hong Kong7574/06M
HKU5/CRF/08
Funding Information:

This study was supported by the General Research Fund (7574/06M) and Collaborative Research Fund (HKU5/CRF/08) of the Research Grant Council Hong Kong. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References
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DC FieldValueLanguage
dc.contributor.authorSun, CKen_HK
dc.contributor.authorNg, KTen_HK
dc.contributor.authorLim, ZXen_HK
dc.contributor.authorCheng, Qen_HK
dc.contributor.authorLo, CMen_HK
dc.contributor.authorPoon, RTen_HK
dc.contributor.authorMan, Ken_HK
dc.contributor.authorWong, Nen_HK
dc.contributor.authorFan, STen_HK
dc.date.accessioned2011-07-27T01:36:32Z-
dc.date.available2011-07-27T01:36:32Z-
dc.date.issued2011en_HK
dc.identifier.citationPlos One, 2011, v. 6 n. 4en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/135527-
dc.description.abstractAims: Proline-rich tyrosine kinase 2 (Pyk2), a non-receptor tyrosine kinase of the focal adhesion kinase (FAK) family, is up-regulated in more than 60% of the tumors of hepatocellular carcinoma (HCC) patients. Forced overexpression of Pyk2 can promote the proliferation and invasion of HCC cells. In this study, we aimed to explore the underlying molecular mechanism of Pyk2-mediated cell migration of HCC cells. Methodology/Principal Findings: We demonstrated that Pyk2 transformed the epithelial HCC cell line Hep3B into a mesenchymal phenotype via the induction of epithelial to mesenchymal transition (EMT), signified by the up-regulation of membrane ruffle formation, activation of Rac/Rho GTPases, down-regulation of epithelial genes E-cadherin and cytokeratin as well as promotion of cell motility in presence of lysophosphatidic acid (LPA). Suppression of Pyk2 by overexpression of dominant negative PRNK domain in the metastatic HCC cell line MHCC97L transformed its fibroblastoid phenotype to an epithelial phenotype with up-regulation of epithelial genes, down-regulation of mesenchymal genes N-cadherin and STAT5b, and reduction of LPA-induced membrane ruffle formation and cell motility. Moreover, overexpression of Pyk2 in Hep3B cells promoted the phosphorylation and localization of mesenchymal gene Hic-5 onto cell membrane while suppression of Pyk2 in MHCC97L cells attenuated its phosphorylation and localization. Conclusion: These data provided new evidence of the underlying mechanism of Pyk2 in controlling cell motility of HCC cells through regulation of genes associated with EMT. © 2011 Sun 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.subject.meshCarcinoma, Hepatocellular - enzymology - pathology - ultrastructure-
dc.subject.meshCell Movement - physiology-
dc.subject.meshEpithelial-Mesenchymal Transition - physiology-
dc.subject.meshFocal Adhesion Kinase 2 - metabolism - physiology-
dc.subject.meshLiver Neoplasms - enzymology - pathology - ultrastructure-
dc.titleProline-rich tyrosine kinase 2 (Pyk2) promotes cell motility of hepatocellular carcinoma through induction of epithelial to mesenchymal transitionen_HK
dc.typeArticleen_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.emailMan, K: kwanman@hku.hken_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.authorityNg, KT=rp01720en_HK
dc.identifier.authorityLo, CM=rp00412en_HK
dc.identifier.authorityPoon, RT=rp00446en_HK
dc.identifier.authorityMan, K=rp00417en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0018878en_HK
dc.identifier.pmid21533080-
dc.identifier.pmcidPMC3080371-
dc.identifier.scopuseid_2-s2.0-79955402374en_HK
dc.identifier.hkuros187505en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79955402374&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume6en_HK
dc.identifier.issue4en_HK
dc.identifier.spagee18878en_US
dc.identifier.epagee18878en_US
dc.identifier.isiWOS:000289719400033-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectLiver Transplantation Research Centre: A Multidisciplinary Study for Liver Graft Injury-
dc.identifier.scopusauthoridSun, CK=7404248685en_HK
dc.identifier.scopusauthoridNg, KT=7403178513en_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.scopusauthoridMan, K=7101754072en_HK
dc.identifier.scopusauthoridWong, N=7202836653en_HK
dc.identifier.scopusauthoridFan, ST=7402678224en_HK

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