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Article: Overexpression of EIF5A2 promotes colorectal carcinoma cell aggressiveness by upregulating MTA1 through C-myc to induce epithelial-mesenchymaltransition

TitleOverexpression of EIF5A2 promotes colorectal carcinoma cell aggressiveness by upregulating MTA1 through C-myc to induce epithelial-mesenchymaltransition
Authors
Issue Date2012
PublisherBMJ Publishing Group. The Journal's web site is located at http://gut.bmjjournals.com/
Citation
Gut, 2012, v. 61 n. 4, p. 562-575 How to Cite?
AbstractBACKGROUND AND AIMS: The authors have previously isolated a putative oncogene, eukaryotic initiation factor 5A2 (EIF5A2) from 3q26. In this study, EIF5A2 was characterised for its role in colorectal carcinoma (CRC) aggressiveness and underlying molecular mechanisms. METHODS: The expression dynamics of EIF5A2 were examined by immunohistochemistry in a cohort of carcinomatous and non-neoplastic colorectal tissues and cells. A series of in-vivo and in-vitro assays was performed to elucidate the function of EIF5A2 in CRC and its underlying mechanisms. RESULTS: The overexpression of EIF5A2 was examined by immunohistochemistry in 102/229 (44.5%) CRC patients, and it was significantly correlated with tumour metastasis and determined to be an independent predictor of shortened survival (p<0.05). Ectopic overexpression of EIF5A2 in CRC cells enhanced cell motility and invasion in vitro and tumour metastasis in vivo, and induced epithelial-mesenchymal transition (EMT). The depletion of EIF5A2 expression prevented CRC cell invasiveness and inhibited EMT. Importantly, the metastasis-associated protein 1 (MTA1) gene was identified as a potential downstream target of EIF5A2 in CRC cells, and knockdown of MTA1 eliminated the augmentation of carcinoma cell migration, invasion and EMT by ectopic EIF5A2. The overexpression of EIF5A2 in CRC cells substantially enhanced the enrichment of c-myc on the promoter of MTA1, and MTA1 upregulation by EIF5A2 was partly dependent on c-myc. CONCLUSION: The data suggest that EIF5A2 plays an important oncogenic role in CRC aggressiveness by the upregulation of MTA1 to induce EMT, and EIF5A2 could be employed as a novel prognostic marker and/or effective therapeutic target for CRC.
Persistent Identifierhttp://hdl.handle.net/10722/150854
ISSN
2014 Impact Factor: 14.660
ISI Accession Number ID
Funding AgencyGrant Number
Nature Science Foundation of China30972884
973 Project of China2010CB529400
2010CB912802
Sun Yat-Sen University Cancer Center303045134001
Funding Information:

This work is supported by grants from the Nature Science Foundation of China (no 30972884), the 973 Project of China (2010CB529400 and 2010CB912802) and the Program for Excellent Young Talents in Sun Yat-Sen University Cancer Center (no 303045134001).

References

 

DC FieldValueLanguage
dc.contributor.authorZhu, Wen_HK
dc.contributor.authorCai, MYen_HK
dc.contributor.authorTong, ZTen_HK
dc.contributor.authorDong, SSen_HK
dc.contributor.authorMai, SJen_HK
dc.contributor.authorLiao, YJen_HK
dc.contributor.authorBian, XWen_HK
dc.contributor.authorLin, MCen_HK
dc.contributor.authorKung, HFen_HK
dc.contributor.authorZeng, YXen_HK
dc.contributor.authorGuan, XYen_HK
dc.contributor.authorXie, Den_HK
dc.date.accessioned2012-06-26T06:12:35Z-
dc.date.available2012-06-26T06:12:35Z-
dc.date.issued2012en_HK
dc.identifier.citationGut, 2012, v. 61 n. 4, p. 562-575en_HK
dc.identifier.issn0017-5749en_HK
dc.identifier.urihttp://hdl.handle.net/10722/150854-
dc.description.abstractBACKGROUND AND AIMS: The authors have previously isolated a putative oncogene, eukaryotic initiation factor 5A2 (EIF5A2) from 3q26. In this study, EIF5A2 was characterised for its role in colorectal carcinoma (CRC) aggressiveness and underlying molecular mechanisms. METHODS: The expression dynamics of EIF5A2 were examined by immunohistochemistry in a cohort of carcinomatous and non-neoplastic colorectal tissues and cells. A series of in-vivo and in-vitro assays was performed to elucidate the function of EIF5A2 in CRC and its underlying mechanisms. RESULTS: The overexpression of EIF5A2 was examined by immunohistochemistry in 102/229 (44.5%) CRC patients, and it was significantly correlated with tumour metastasis and determined to be an independent predictor of shortened survival (p<0.05). Ectopic overexpression of EIF5A2 in CRC cells enhanced cell motility and invasion in vitro and tumour metastasis in vivo, and induced epithelial-mesenchymal transition (EMT). The depletion of EIF5A2 expression prevented CRC cell invasiveness and inhibited EMT. Importantly, the metastasis-associated protein 1 (MTA1) gene was identified as a potential downstream target of EIF5A2 in CRC cells, and knockdown of MTA1 eliminated the augmentation of carcinoma cell migration, invasion and EMT by ectopic EIF5A2. The overexpression of EIF5A2 in CRC cells substantially enhanced the enrichment of c-myc on the promoter of MTA1, and MTA1 upregulation by EIF5A2 was partly dependent on c-myc. CONCLUSION: The data suggest that EIF5A2 plays an important oncogenic role in CRC aggressiveness by the upregulation of MTA1 to induce EMT, and EIF5A2 could be employed as a novel prognostic marker and/or effective therapeutic target for CRC.en_HK
dc.languageengen_US
dc.publisherBMJ Publishing Group. The Journal's web site is located at http://gut.bmjjournals.com/en_HK
dc.relation.ispartofGuten_HK
dc.rightsGut. Copyright © BMJ Publishing Group.-
dc.rightsThis article has been accepted for publication in [Gut]. The definitive copyedited, typeset version [Gut, 2012, v. 61 n. 4, p. 562-575] is available online at: www.gut.bmj.com-
dc.subject.meshColorectal Neoplasms - metabolism - pathologyen_US
dc.subject.meshEpithelial-Mesenchymal Transition - physiologyen_US
dc.subject.meshHistone Deacetylases - biosynthesisen_US
dc.subject.meshPeptide Initiation Factors - metabolism - physiologyen_US
dc.subject.meshRNA-Binding Proteins - metabolism - physiologyen_US
dc.titleOverexpression of EIF5A2 promotes colorectal carcinoma cell aggressiveness by upregulating MTA1 through C-myc to induce epithelial-mesenchymaltransitionen_HK
dc.typeArticleen_HK
dc.identifier.emailDong, SS: dongss@hku.hken_HK
dc.identifier.emailLin, MC: mcllin@hkucc.hku.hken_HK
dc.identifier.emailGuan, XY: xyguan@hkucc.hku.hk-
dc.identifier.emailXie, D: xied@mail.sysu.edu.cn-
dc.identifier.authorityLin, MC=rp00746en_HK
dc.identifier.authorityGuan, XY=rp00454en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1136/gutjnl-2011-300207en_HK
dc.identifier.pmid21813470en_HK
dc.identifier.scopuseid_2-s2.0-84857798740en_HK
dc.identifier.hkuros203482-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84857798740&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume61en_HK
dc.identifier.issue4en_HK
dc.identifier.spage562en_HK
dc.identifier.epage575en_HK
dc.identifier.isiWOS:000300955000014-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridXie, D=35070710200en_HK
dc.identifier.scopusauthoridGuan, XY=7201463221en_HK
dc.identifier.scopusauthoridZeng, YX=7402981579en_HK
dc.identifier.scopusauthoridKung, HF=7402514190en_HK
dc.identifier.scopusauthoridLin, MC=7404816359en_HK
dc.identifier.scopusauthoridBian, XW=7103023096en_HK
dc.identifier.scopusauthoridLiao, YJ=36114448500en_HK
dc.identifier.scopusauthoridMai, SJ=36780688900en_HK
dc.identifier.scopusauthoridDong, SS=35788109500en_HK
dc.identifier.scopusauthoridTong, ZT=36747652800en_HK
dc.identifier.scopusauthoridCai, MY=23388510500en_HK
dc.identifier.scopusauthoridZhu, W=55097876100en_HK
dc.identifier.citeulike11743477-

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