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Article: Rac activation is associated with hepatocellular carcinoma metastasis by up-regulation of vascular endothelial growth factor expression

TitleRac activation is associated with hepatocellular carcinoma metastasis by up-regulation of vascular endothelial growth factor expression
Authors
Issue Date2006
PublisherAmerican Association for Cancer Research.
Citation
Clinical Cancer Research, 2006, v. 12 n. 17, p. 5082-5089 How to Cite?
AbstractPurpose: Hepatocellular carcinoma (HCC) is associated with a propensity for vascular invasion and metastasis, which contribute to poor prognosis. Angiogenesis is a crucial process contributing to tumor growth and metastasis. Recently, Rac has been suggested to play a role in angiogenesis. However, the actual role of Rac in HCC angiogenesis remains unclear. Given that vascular endothelial growth factor (VEGF) is an important angiogenic factor in HCC, the purpose of this study was to evaluate the possible correlation between Rac activation and VEGF expression in HCC tumor samples, as well as the mechanism involved in Rac-induced HCC angiogenesis. Experimental Design: We evaluated Rac and VEGF expression in the HCC tissue microarray of paired primary and metastatic HCC samples using immunohistochemical staining. The role of Rac-induced HCC angiogenesis was also evaluated in vitro in HCC cell lines. Results: We first showed that activation of Rac was correlated with HCC metastasis (P < 0.001), and its expression was significantly correlated with VEGF expression by tissue microarray. Ectopic Rac-dominant active transfection in Hep3B cells increased VEGF secretion, which induced the morphologic change and proliferation of human umbilical vein endothelial cells, resulting in the promotion of angiogenesis. Rac induced the transcriptional activation of VEGF by direct interaction with hypoxia-inducible factor-1α (HIF-1α) expression. In hypoxic conditions, Rac promoted angiogenesis through an increase in HIF-1α stabilization. Conclusion: This study shows that Rac is a novel angiogenic factor for HCC through the enhancement of HIF-1α protein stability, which provides a possible therapeutic target in the development of inhibitors of angiogenesis. © 2006 American Association for Cancer Research.
Persistent Identifierhttp://hdl.handle.net/10722/130953
ISSN
2015 Impact Factor: 8.738
2015 SCImago Journal Rankings: 5.314
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLee, TKen_HK
dc.contributor.authorPoon, RTPen_HK
dc.contributor.authorYuen, APen_HK
dc.contributor.authorMan, Ken_HK
dc.contributor.authorZhen, FYen_HK
dc.contributor.authorXin, YGen_HK
dc.contributor.authorSheung, TFen_HK
dc.date.accessioned2011-01-13T04:21:36Z-
dc.date.available2011-01-13T04:21:36Z-
dc.date.issued2006en_HK
dc.identifier.citationClinical Cancer Research, 2006, v. 12 n. 17, p. 5082-5089en_HK
dc.identifier.issn1078-0432en_HK
dc.identifier.urihttp://hdl.handle.net/10722/130953-
dc.description.abstractPurpose: Hepatocellular carcinoma (HCC) is associated with a propensity for vascular invasion and metastasis, which contribute to poor prognosis. Angiogenesis is a crucial process contributing to tumor growth and metastasis. Recently, Rac has been suggested to play a role in angiogenesis. However, the actual role of Rac in HCC angiogenesis remains unclear. Given that vascular endothelial growth factor (VEGF) is an important angiogenic factor in HCC, the purpose of this study was to evaluate the possible correlation between Rac activation and VEGF expression in HCC tumor samples, as well as the mechanism involved in Rac-induced HCC angiogenesis. Experimental Design: We evaluated Rac and VEGF expression in the HCC tissue microarray of paired primary and metastatic HCC samples using immunohistochemical staining. The role of Rac-induced HCC angiogenesis was also evaluated in vitro in HCC cell lines. Results: We first showed that activation of Rac was correlated with HCC metastasis (P < 0.001), and its expression was significantly correlated with VEGF expression by tissue microarray. Ectopic Rac-dominant active transfection in Hep3B cells increased VEGF secretion, which induced the morphologic change and proliferation of human umbilical vein endothelial cells, resulting in the promotion of angiogenesis. Rac induced the transcriptional activation of VEGF by direct interaction with hypoxia-inducible factor-1α (HIF-1α) expression. In hypoxic conditions, Rac promoted angiogenesis through an increase in HIF-1α stabilization. Conclusion: This study shows that Rac is a novel angiogenic factor for HCC through the enhancement of HIF-1α protein stability, which provides a possible therapeutic target in the development of inhibitors of angiogenesis. © 2006 American Association for Cancer Research.en_HK
dc.languageeng-
dc.publisherAmerican Association for Cancer Research.-
dc.relation.ispartofClinical Cancer Researchen_HK
dc.subject.meshCarcinoma, Hepatocellular - metabolism - pathology - secondary-
dc.subject.meshCell Line, Tumor-
dc.subject.meshLiver Neoplasms - metabolism - pathology-
dc.subject.meshVascular Endothelial Growth Factors - biosynthesis - metabolism-
dc.subject.meshrac GTP-Binding Proteins - metabolism-
dc.titleRac activation is associated with hepatocellular carcinoma metastasis by up-regulation of vascular endothelial growth factor expressionen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1078-0432&volume=12&issue=17&spage=5082&epage=5089&date=01&atitle=Rac+Activation+Is+Associated+with+Hepatocellular+Carcinoma+Metastasis+by+Up-regulation+of+Vascular+Endothelial+Growth+Factor+Expression-
dc.identifier.emailLee, TK:tkwlee@hkucc.hku.hken_HK
dc.identifier.emailPoon, RTP:poontp@hkucc.hku.hken_HK
dc.identifier.emailMan, K:kwanman@hkucc.hku.hken_HK
dc.identifier.emailXin, YG:xyguan@hkucc.hku.hken_HK
dc.identifier.authorityLee, TK=rp00447en_HK
dc.identifier.authorityPoon, RTP=rp00446en_HK
dc.identifier.authorityMan, K=rp00417en_HK
dc.identifier.authorityXin, YG=rp00454en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1158/1078-0432.CCR-05-2794en_HK
dc.identifier.pmid16951224-
dc.identifier.scopuseid_2-s2.0-33749000324en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33749000324&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume12en_HK
dc.identifier.issue17en_HK
dc.identifier.spage5082en_HK
dc.identifier.epage5089en_HK
dc.identifier.isiWOS:000240392000014-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLee, TK=7501439435en_HK
dc.identifier.scopusauthoridPoon, RTP=7103097223en_HK
dc.identifier.scopusauthoridYuen, AP=7006290111en_HK
dc.identifier.scopusauthoridMan, K=7101754072en_HK
dc.identifier.scopusauthoridZhen, FY=14018809600en_HK
dc.identifier.scopusauthoridXin, YG=7201463221en_HK
dc.identifier.scopusauthoridSheung, TF=6506234707en_HK

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