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- Publisher Website: 10.1172/JCI40665
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- PMID: 20335658
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Article: CHD1L promotes hepatocellular carcinoma progression and metastasis in mice and is associated with these processes in human patients
Title | CHD1L promotes hepatocellular carcinoma progression and metastasis in mice and is associated with these processes in human patients | ||||||||||
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Authors | |||||||||||
Issue Date | 2010 | ||||||||||
Publisher | American Society for Clinical Investigation. The Journal's web site is located at http://www.jci.org | ||||||||||
Citation | Journal Of Clinical Investigation, 2010, v. 120 n. 4, p. 1178-1191 How to Cite? | ||||||||||
Abstract | Chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) is a recently identified oncogene localized at 1q21, a frequently amplified region in hepatocellular carcinoma (HCC). To explore its oncogenic mechanisms, we set out to identify CHD1L-regulated genes using a chromatin immunoprecipitation-based (ChIP-based) cloning strategy in a human HCC cell line. We then further characterized 1 identified gene, ARHGEF9, which encodes a specific guanine nucleotide exchange factor (GEF) for the Rho small GTPase Cdc42. Overexpression of ARHGEF9 was detected in approximately half the human HCC samples analyzed and positively correlated with CHD1L overexpression. In vitro and in vivo functional studies in mice showed that CHD1L contributed to tumor cell migration, invasion, and metastasis by increasing cell motility and inducing filopodia formation and epithelial-mesenchymal transition (EMT) via ARHGEF9-mediated Cdc42 activation. Silencing ARHGEF9 expression by RNAi effectively abolished the invasive and metastatic abilities of CHD1L in mice. Furthermore, investigation of clinical HCC specimens showed that CHD1L and ARHGEF9 were markedly overexpressed in metastatic HCC tissue compared with healthy tissue. Increased expression of CHD1L was often observed at the invasive front of HCC tumors and correlated with venous infiltration, microsatellite tumor nodule formation, and poor disease-free survival. These findings suggest that CHD1L-ARHGEF9-Cdc42-EMT might be a novel pathway involved in HCC progression and metastasis. | ||||||||||
Persistent Identifier | http://hdl.handle.net/10722/71912 | ||||||||||
ISSN | 2023 Impact Factor: 13.3 2023 SCImago Journal Rankings: 4.833 | ||||||||||
PubMed Central ID | |||||||||||
ISI Accession Number ID |
Funding Information: This work was supported by a Hong Kong Research Grant Council Grant (HKU 7656/07M), Hong Kong Research Grant Council Central Allocations (HKU 1/06C and HKU5/CRF/08), the "Hundred Talents Program" at Sun Yat-sen University (85000-3171311), the Major State Basic Research Program of China (2006CB910104), and a grant from the National Natural Science Foundation of China (30772475). | ||||||||||
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DC Field | Value | Language |
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dc.contributor.author | Chen, L | en_HK |
dc.contributor.author | Chan, THM | en_HK |
dc.contributor.author | Yuan, YF | en_HK |
dc.contributor.author | Hu, L | en_HK |
dc.contributor.author | Huang, J | en_HK |
dc.contributor.author | Ma, S | en_HK |
dc.contributor.author | Wang, J | en_HK |
dc.contributor.author | Dong, SS | en_HK |
dc.contributor.author | Tang, KH | en_HK |
dc.contributor.author | Xie, D | en_HK |
dc.contributor.author | Li, Y | en_HK |
dc.contributor.author | Guan, XY | en_HK |
dc.date.accessioned | 2010-09-06T06:36:25Z | - |
dc.date.available | 2010-09-06T06:36:25Z | - |
dc.date.issued | 2010 | en_HK |
dc.identifier.citation | Journal Of Clinical Investigation, 2010, v. 120 n. 4, p. 1178-1191 | en_HK |
dc.identifier.issn | 0021-9738 | en_HK |
dc.identifier.uri | http://hdl.handle.net/10722/71912 | - |
dc.description.abstract | Chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) is a recently identified oncogene localized at 1q21, a frequently amplified region in hepatocellular carcinoma (HCC). To explore its oncogenic mechanisms, we set out to identify CHD1L-regulated genes using a chromatin immunoprecipitation-based (ChIP-based) cloning strategy in a human HCC cell line. We then further characterized 1 identified gene, ARHGEF9, which encodes a specific guanine nucleotide exchange factor (GEF) for the Rho small GTPase Cdc42. Overexpression of ARHGEF9 was detected in approximately half the human HCC samples analyzed and positively correlated with CHD1L overexpression. In vitro and in vivo functional studies in mice showed that CHD1L contributed to tumor cell migration, invasion, and metastasis by increasing cell motility and inducing filopodia formation and epithelial-mesenchymal transition (EMT) via ARHGEF9-mediated Cdc42 activation. Silencing ARHGEF9 expression by RNAi effectively abolished the invasive and metastatic abilities of CHD1L in mice. Furthermore, investigation of clinical HCC specimens showed that CHD1L and ARHGEF9 were markedly overexpressed in metastatic HCC tissue compared with healthy tissue. Increased expression of CHD1L was often observed at the invasive front of HCC tumors and correlated with venous infiltration, microsatellite tumor nodule formation, and poor disease-free survival. These findings suggest that CHD1L-ARHGEF9-Cdc42-EMT might be a novel pathway involved in HCC progression and metastasis. | en_HK |
dc.language | eng | en_HK |
dc.publisher | American Society for Clinical Investigation. The Journal's web site is located at http://www.jci.org | en_HK |
dc.relation.ispartof | Journal of Clinical Investigation | en_HK |
dc.subject.mesh | Animals | - |
dc.subject.mesh | Carcinoma, Hepatocellular - etiology - pathology | - |
dc.subject.mesh | DNA Helicases - physiology | - |
dc.subject.mesh | DNA-Binding Proteins - physiology | - |
dc.subject.mesh | Liver Neoplasms - etiology - pathology | - |
dc.title | CHD1L promotes hepatocellular carcinoma progression and metastasis in mice and is associated with these processes in human patients | en_HK |
dc.type | Article | en_HK |
dc.identifier.openurl | http://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-9738&volume=120&issue=4&spage=1178&epage=1191&date=2010&atitle=CHD1L+promotes+hepatocellular+carcinoma+progression+and+metastasis+in+mice+and+is+associated+with+these+processes+in+human+patients | en_HK |
dc.identifier.email | Ma, S:sma@pathology.hku.hk | en_HK |
dc.identifier.email | Guan, XY:xyguan@hkucc.hku.hk | en_HK |
dc.identifier.authority | Ma, S=rp00506 | en_HK |
dc.identifier.authority | Guan, XY=rp00454 | en_HK |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1172/JCI40665 | en_HK |
dc.identifier.pmid | 20335658 | - |
dc.identifier.pmcid | PMC2846051 | - |
dc.identifier.scopus | eid_2-s2.0-77951176116 | en_HK |
dc.identifier.hkuros | 169645 | en_HK |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-77951176116&selection=ref&src=s&origin=recordpage | en_HK |
dc.identifier.volume | 120 | en_HK |
dc.identifier.issue | 4 | en_HK |
dc.identifier.spage | 1178 | en_HK |
dc.identifier.epage | 1191 | en_HK |
dc.identifier.eissn | 1558-8238 | - |
dc.identifier.isi | WOS:000276258100028 | - |
dc.publisher.place | United States | en_HK |
dc.relation.project | Molecular pathology of liver cancer - a multidisciplinary study | - |
dc.relation.project | Liver Transplantation Research Centre: A Multidisciplinary Study for Liver Graft Injury | - |
dc.identifier.scopusauthorid | Chen, L=23569135400 | en_HK |
dc.identifier.scopusauthorid | Chan, THM=26431726400 | en_HK |
dc.identifier.scopusauthorid | Yuan, YF=7402708979 | en_HK |
dc.identifier.scopusauthorid | Hu, L=34770075600 | en_HK |
dc.identifier.scopusauthorid | Huang, J=24467982900 | en_HK |
dc.identifier.scopusauthorid | Ma, S=16444895800 | en_HK |
dc.identifier.scopusauthorid | Wang, J=24371445200 | en_HK |
dc.identifier.scopusauthorid | Dong, SS=35788109500 | en_HK |
dc.identifier.scopusauthorid | Tang, KH=24781597200 | en_HK |
dc.identifier.scopusauthorid | Xie, D=35070710200 | en_HK |
dc.identifier.scopusauthorid | Li, Y=36078824800 | en_HK |
dc.identifier.scopusauthorid | Guan, XY=7201463221 | en_HK |
dc.identifier.issnl | 0021-9738 | - |