File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: P21-activated protein kinase is overexpressed in hepatocellular carcinoma and enhances cancer metastasis involving c-Jun NH2-terminal kinase activation and paxillin phosphorylation

TitleP21-activated protein kinase is overexpressed in hepatocellular carcinoma and enhances cancer metastasis involving c-Jun NH2-terminal kinase activation and paxillin phosphorylation
Authors
Issue Date2007
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2007, v. 67 n. 8, p. 3601-3608 How to Cite?
AbstractHepatocellular carcinoma (HCC) is one of the major malignancies in the world. The prognosis of HCC is poor, due to frequent intrahepatic metastasis and tumor recurrence. P21-activated protein kinase (Pak1), a main downstream effector of small Rho GTPases, Rac1 and Cdc42, plays an important role in the regulation of cell morphogenesis, motility, mitosis, and angiogenesis. Here, we show that Pak1 gene was overexpressed in human HCCs. Overexpression of Pak1 in human HCCs was associated with more aggressive tumor behavior in terms of more metastatic phenotype and more advanced tumor stages. In addition, HCC cell line stably expressing Pak1 displayed increased cell motility rates and, conversely, knockdown of endogenous Pak1 expression by small interfering RNA reduced the migration rates of HCC cells. In an established metastatic HCC cell line, we found that Pak1 was overexpressed compared with its primary HCC cell line and this overexpression was associated with higher cell motility. Importantly, we found that c-Jun NH2-terminal kinase (JNK) was activated in HCC cell lines overexpressing Pak1. Inhibition of the JNK activity by chemical inhibitor significantly reduced the migration rates of HCC cells via attenuation of paxillin phosphorylation at Ser178. In conclusion, our results document that Pak1 is overexpressed in HCCs and plays an important role in the metastasis of HCC. The mechanism by which Pak1 induces cancer metastasis may involve activation of JNK and phosphorylation of paxillin. ©2007 American Association for Cancer Research.
Persistent Identifierhttp://hdl.handle.net/10722/67427
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChing, YPen_HK
dc.contributor.authorLeong, VYLen_HK
dc.contributor.authorLee, MFen_HK
dc.contributor.authorXu, HTen_HK
dc.contributor.authorJin, DYen_HK
dc.contributor.authorNg, IOLen_HK
dc.date.accessioned2010-09-06T05:55:02Z-
dc.date.available2010-09-06T05:55:02Z-
dc.date.issued2007en_HK
dc.identifier.citationCancer Research, 2007, v. 67 n. 8, p. 3601-3608en_HK
dc.identifier.issn0008-5472en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67427-
dc.description.abstractHepatocellular carcinoma (HCC) is one of the major malignancies in the world. The prognosis of HCC is poor, due to frequent intrahepatic metastasis and tumor recurrence. P21-activated protein kinase (Pak1), a main downstream effector of small Rho GTPases, Rac1 and Cdc42, plays an important role in the regulation of cell morphogenesis, motility, mitosis, and angiogenesis. Here, we show that Pak1 gene was overexpressed in human HCCs. Overexpression of Pak1 in human HCCs was associated with more aggressive tumor behavior in terms of more metastatic phenotype and more advanced tumor stages. In addition, HCC cell line stably expressing Pak1 displayed increased cell motility rates and, conversely, knockdown of endogenous Pak1 expression by small interfering RNA reduced the migration rates of HCC cells. In an established metastatic HCC cell line, we found that Pak1 was overexpressed compared with its primary HCC cell line and this overexpression was associated with higher cell motility. Importantly, we found that c-Jun NH2-terminal kinase (JNK) was activated in HCC cell lines overexpressing Pak1. Inhibition of the JNK activity by chemical inhibitor significantly reduced the migration rates of HCC cells via attenuation of paxillin phosphorylation at Ser178. In conclusion, our results document that Pak1 is overexpressed in HCCs and plays an important role in the metastasis of HCC. The mechanism by which Pak1 induces cancer metastasis may involve activation of JNK and phosphorylation of paxillin. ©2007 American Association for Cancer Research.en_HK
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/en_HK
dc.relation.ispartofCancer Researchen_HK
dc.subject.meshCarcinoma, Hepatocellular - enzymology - genetics - metabolism - pathologyen_HK
dc.subject.meshCell Line, Tumoren_HK
dc.subject.meshCell Movement - physiologyen_HK
dc.subject.meshEnzyme Activationen_HK
dc.subject.meshHumansen_HK
dc.subject.meshJNK Mitogen-Activated Protein Kinases - metabolismen_HK
dc.subject.meshLiver Neoplasms - enzymology - genetics - metabolism - pathologyen_HK
dc.subject.meshNeoplasm Metastasisen_HK
dc.subject.meshPaxillin - metabolismen_HK
dc.subject.meshPhosphorylationen_HK
dc.subject.meshProtein-Serine-Threonine Kinases - biosynthesis - genetics - metabolismen_HK
dc.subject.meshp21-Activated Kinasesen_HK
dc.titleP21-activated protein kinase is overexpressed in hepatocellular carcinoma and enhances cancer metastasis involving c-Jun NH2-terminal kinase activation and paxillin phosphorylationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0008-5472&volume=67&spage=3601&epage=3608&date=2007&atitle=P21-activated+protein+kinase+is+overexpressed+in+hepatocellular+carcinoma+and+enhances+cancer+metastasis+involving+c-Jun+NH2-terminal+kinase+activation+and+paxillin+phosphorylation.+en_HK
dc.identifier.emailChing, YP:ypching@hku.hken_HK
dc.identifier.emailJin, DY:dyjin@hkucc.hku.hken_HK
dc.identifier.emailNg, IOL:iolng@hkucc.hku.hken_HK
dc.identifier.authorityChing, YP=rp00469en_HK
dc.identifier.authorityJin, DY=rp00452en_HK
dc.identifier.authorityNg, IOL=rp00335en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1158/0008-5472.CAN-06-3994en_HK
dc.identifier.pmid17440071-
dc.identifier.scopuseid_2-s2.0-34248531653en_HK
dc.identifier.hkuros126751en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-34248531653&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume67en_HK
dc.identifier.issue8en_HK
dc.identifier.spage3601en_HK
dc.identifier.epage3608en_HK
dc.identifier.isiWOS:000245779600020-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridChing, YP=7005431277en_HK
dc.identifier.scopusauthoridLeong, VYL=36832636400en_HK
dc.identifier.scopusauthoridLee, MF=8277448500en_HK
dc.identifier.scopusauthoridXu, HT=16311244600en_HK
dc.identifier.scopusauthoridJin, DY=7201973614en_HK
dc.identifier.scopusauthoridNg, IOL=7102753722en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats