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Article: Overexpression of eukaryotic initiation factor 5A2 enhances cell motility and promotes tumor metastasis in hepatocellular carcinoma

TitleOverexpression of eukaryotic initiation factor 5A2 enhances cell motility and promotes tumor metastasis in hepatocellular carcinoma
Authors
Issue Date2010
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/
Citation
Hepatology, 2010, v. 51 n. 4, p. 1255-1263 How to Cite?
AbstractA high incidence of tumor recurrence and metastasis has been reported in hepatocellular carcinoma (HCC) patients; however, the underlying molecular mechanisms are largely unknown. In the present study a novel metastasis-related gene, eukaryotic initiation factor 5A2 (EIF5A2), was characterized for its role in HCC metastasis and underlying molecular mechanisms. Overexpression of EIF5A2 messenger RNA (mRNA) was detected in 50/81 (61.7%) of HCCs, which was significantly higher than those in nontumorous liver tissues. Compared with matched primary HCC, higher expression of EIF5A2 protein was observed in 25/47 (53.2%) of metastatic tumors. Functional studies found that ectopic expression of EIF5A2 could enhance cancer cell migration and invasion in vitro and tumor metastasis in vivo in an experimental mouse model. Moreover, inhibition of EIF5A by small interfering RNA (siRNA) or deoxyhypusine synthase (DHPS) inhibitor GC7, which inhibits EIF5A2 maturation, could effectively decrease cell motility. Further study found that EIF5A2 was able to induce epithelial-mesenchymal transition (EMT), a key event in tumor invasion and metastasis, characterized by down-regulation of epithelial markers (E-cadherin and β-catenin) and up-regulation of mesenchymal markers (fibronectin, N-cadherin, β-SMA, and vimentin). In addition, EIF5A2 could also activate RhoA/Rac1 to stimulate the formation of stress fiber and lamellipodia. Conclusion: EIF5A2 plays an important role in HCC invasion and metastasis by inducing EMT, as well as stimulating cytoskeleton rearrangement through activation of RhoA and Rac1. Copyright © 2010 by the American Association for the Study of Liver Diseases.
Persistent Identifierhttp://hdl.handle.net/10722/68259
ISSN
2015 Impact Factor: 11.711
2015 SCImago Journal Rankings: 4.752
ISI Accession Number ID
Funding AgencyGrant Number
Research Grant CouncilHKU 765670731
Research Grant Council Central AllocationHKU1/06C
HKUS/CRF/08
National Natural Science Foundation of China30772475
Major State Basic Research Program of China2006CB910104
Sun Yat-Sen University85000-3171311
Funding Information:

Supported by grants from Research Grant Council (HKU 765670731), Research Grant Council Central Allocation (HKU1/06C and HKUS/CRF/08), National Natural Science Foundation of China (No. 30772475), the Major State Basic Research Program of China (2006CB910104), and Sun Yat-Sen University "Hundred Talents Program" (85000-3171311).

References

 

DC FieldValueLanguage
dc.contributor.authorTang, DJen_HK
dc.contributor.authorDong, SSen_HK
dc.contributor.authorMa, NFen_HK
dc.contributor.authorXie, Den_HK
dc.contributor.authorChen, Len_HK
dc.contributor.authorFu, Len_HK
dc.contributor.authorLau, SHen_HK
dc.contributor.authorLi, Yen_HK
dc.contributor.authorGuan, XYen_HK
dc.date.accessioned2010-09-06T06:02:52Z-
dc.date.available2010-09-06T06:02:52Z-
dc.date.issued2010en_HK
dc.identifier.citationHepatology, 2010, v. 51 n. 4, p. 1255-1263en_HK
dc.identifier.issn0270-9139en_HK
dc.identifier.urihttp://hdl.handle.net/10722/68259-
dc.description.abstractA high incidence of tumor recurrence and metastasis has been reported in hepatocellular carcinoma (HCC) patients; however, the underlying molecular mechanisms are largely unknown. In the present study a novel metastasis-related gene, eukaryotic initiation factor 5A2 (EIF5A2), was characterized for its role in HCC metastasis and underlying molecular mechanisms. Overexpression of EIF5A2 messenger RNA (mRNA) was detected in 50/81 (61.7%) of HCCs, which was significantly higher than those in nontumorous liver tissues. Compared with matched primary HCC, higher expression of EIF5A2 protein was observed in 25/47 (53.2%) of metastatic tumors. Functional studies found that ectopic expression of EIF5A2 could enhance cancer cell migration and invasion in vitro and tumor metastasis in vivo in an experimental mouse model. Moreover, inhibition of EIF5A by small interfering RNA (siRNA) or deoxyhypusine synthase (DHPS) inhibitor GC7, which inhibits EIF5A2 maturation, could effectively decrease cell motility. Further study found that EIF5A2 was able to induce epithelial-mesenchymal transition (EMT), a key event in tumor invasion and metastasis, characterized by down-regulation of epithelial markers (E-cadherin and β-catenin) and up-regulation of mesenchymal markers (fibronectin, N-cadherin, β-SMA, and vimentin). In addition, EIF5A2 could also activate RhoA/Rac1 to stimulate the formation of stress fiber and lamellipodia. Conclusion: EIF5A2 plays an important role in HCC invasion and metastasis by inducing EMT, as well as stimulating cytoskeleton rearrangement through activation of RhoA and Rac1. Copyright © 2010 by the American Association for the Study of Liver Diseases.en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/en_HK
dc.relation.ispartofHepatologyen_HK
dc.rightsHepatology. Copyright © John Wiley & Sons, Inc.en_HK
dc.subject.meshCarcinoma, Hepatocellular - pathology - secondary-
dc.subject.meshLiver Neoplasms - pathology-
dc.subject.meshPeptide Initiation Factors - antagonists and inhibitors - genetics - physiology-
dc.subject.meshCell Movement-
dc.subject.meshEpithelial Cells - pathology-
dc.titleOverexpression of eukaryotic initiation factor 5A2 enhances cell motility and promotes tumor metastasis in hepatocellular carcinomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0270-9139&volume=51&issue=4&spage=1255&epage=1263&date=2010&atitle=Overexpression+of+eukaryotic+initiation+factor+5A2+enhances+cell+motility+and+promotes+tumor+metastasis+in+hepatocellular+carcinomaen_HK
dc.identifier.emailFu, L:gracefu@graduate.hku.hken_HK
dc.identifier.emailGuan, XY:xyguan@hkucc.hku.hken_HK
dc.identifier.authorityFu, L=rp01435en_HK
dc.identifier.authorityGuan, XY=rp00454en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1002/hep.23451en_HK
dc.identifier.pmid20112425-
dc.identifier.scopuseid_2-s2.0-77950598935en_HK
dc.identifier.hkuros169980en_HK
dc.identifier.hkuros232350-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77950598935&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume51en_HK
dc.identifier.issue4en_HK
dc.identifier.spage1255en_HK
dc.identifier.epage1263en_HK
dc.identifier.eissn1527-3350-
dc.identifier.isiWOS:000276538100022-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridTang, DJ=12752134500en_HK
dc.identifier.scopusauthoridDong, SS=35788109500en_HK
dc.identifier.scopusauthoridMa, NF=35731661400en_HK
dc.identifier.scopusauthoridXie, D=35070710200en_HK
dc.identifier.scopusauthoridChen, L=23569135400en_HK
dc.identifier.scopusauthoridFu, L=22979236700en_HK
dc.identifier.scopusauthoridLau, SH=7401596190en_HK
dc.identifier.scopusauthoridLi, Y=36078824800en_HK
dc.identifier.scopusauthoridGuan, XY=7201463221en_HK

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