Article: Overexpression of EIF5A2 promotes colorectal carcinoma cell aggressiveness by upregulating MTA1 through C-myc to induce epithelial-mesenchymaltransition
| Title | Overexpression of EIF5A2 promotes colorectal carcinoma cell aggressiveness by upregulating MTA1 through C-myc to induce epithelial-mesenchymaltransition | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Authors | Zhu, W2 Cai, MY2 Tong, ZT2 Dong, SS1 Mai, SJ2 Liao, YJ2 Bian, XW3 Lin, MC2 4 Kung, HF2 4 Zeng, YX2 Guan, XY1 2 Xie, D2 | ||||||||
| Issue Date | 2012 | ||||||||
| Publisher | BMJ 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?] DOI: http://dx.doi.org/10.1136/gutjnl-2011-300207 | ||||||||
| Abstract | BACKGROUND 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. | ||||||||
| ISSN | 0017-5749 2011 Impact Factor: 10.111 2011 SCImago Journal Rankings: 0.883 | ||||||||
| DOI | http://dx.doi.org/10.1136/gutjnl-2011-300207 | ||||||||
| ISI Accession Number ID | WOS:000300955000014
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 | References in Scopus |
| dc.contributor.author | Zhu, W | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| dc.contributor.author | Cai, MY | ||||||||
| dc.contributor.author | Tong, ZT | ||||||||
| dc.contributor.author | Dong, SS | ||||||||
| dc.contributor.author | Mai, SJ | ||||||||
| dc.contributor.author | Liao, YJ | ||||||||
| dc.contributor.author | Bian, XW | ||||||||
| dc.contributor.author | Lin, MC | ||||||||
| dc.contributor.author | Kung, HF | ||||||||
| dc.contributor.author | Zeng, YX | ||||||||
| dc.contributor.author | Guan, XY | ||||||||
| dc.contributor.author | Xie, D | ||||||||
| dc.date.accessioned | 2012-06-26T06:12:35Z | ||||||||
| dc.date.available | 2012-06-26T06:12:35Z | ||||||||
| dc.date.issued | 2012 | ||||||||
| dc.description.abstract | BACKGROUND 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. | ||||||||
| dc.description.nature | Link_to_subscribed_fulltext | ||||||||
| dc.identifier.citation | Gut, 2012, v. 61 n. 4, p. 562-575 [How to Cite?] DOI: http://dx.doi.org/10.1136/gutjnl-2011-300207 | ||||||||
| dc.identifier.citeulike | 11743477 | ||||||||
| dc.identifier.doi | http://dx.doi.org/10.1136/gutjnl-2011-300207 | ||||||||
| dc.identifier.epage | 575 | ||||||||
| dc.identifier.hkuros | 203482 | ||||||||
| dc.identifier.isi | WOS:000300955000014
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). | ||||||||
| dc.identifier.issn | 0017-5749 2011 Impact Factor: 10.111 2011 SCImago Journal Rankings: 0.883 | ||||||||
| dc.identifier.issue | 4 | ||||||||
| dc.identifier.pmid | 21813470 | ||||||||
| dc.identifier.scopus | eid_2-s2.0-84857798740 | ||||||||
| dc.identifier.spage | 562 | ||||||||
| dc.identifier.uri | http://hdl.handle.net/10722/150854 | ||||||||
| dc.identifier.volume | 61 | ||||||||
| dc.language | eng | ||||||||
| dc.publisher | BMJ Publishing Group. The Journal's web site is located at http://gut.bmjjournals.com/ | ||||||||
| dc.publisher.place | United Kingdom | ||||||||
| dc.relation.ispartof | Gut | ||||||||
| dc.relation.references | References in Scopus | ||||||||
| dc.rights | Gut. Copyright © BMJ Publishing Group. | ||||||||
| dc.rights | This 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.mesh | Colorectal Neoplasms - metabolism - pathology | ||||||||
| dc.subject.mesh | Epithelial-Mesenchymal Transition - physiology | ||||||||
| dc.subject.mesh | Histone Deacetylases - biosynthesis | ||||||||
| dc.subject.mesh | Peptide Initiation Factors - metabolism - physiology | ||||||||
| dc.subject.mesh | RNA-Binding Proteins - metabolism - physiology | ||||||||
| dc.title | Overexpression of EIF5A2 promotes colorectal carcinoma cell aggressiveness by upregulating MTA1 through C-myc to induce epithelial-mesenchymaltransition | ||||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong
- Sun Yat-Sen University
- Third Military Medical University
- Chinese University of Hong Kong