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Article: Ablation of EIF5A2 induces tumor vasculature remodeling and improves tumor response to chemotherapy via regulation of matrix metalloproteinase 2 expression

TitleAblation of EIF5A2 induces tumor vasculature remodeling and improves tumor response to chemotherapy via regulation of matrix metalloproteinase 2 expression
Authors
Issue Date2014
PublisherImpact Journals LLC. The Journal's web site is located at http://www.impactjournals.com/oncotarget/index.html
Citation
Oncotarget, 2014, v. 5 n. 16, p. 6716-6733 How to Cite?
AbstractHepatocellular carcinoma (HCC) is a highly vascularized tumor with poor clinical outcome. Our previous work has shown that eukaryotic initiation factor 5A2 (EIF5A2) over-expression enhances HCC cell metastasis. In this study, EIF5A2 was identified to be an independent risk factor for poor disease-specific survival among HCC patients. Both in vitro and in vivo assays indicated that ablation of endogenous EIF5A2 inhibited tumor angiogenesis by reducing matrix metalloproteinase 2 (MMP-2) expression. Given that MMP-2 degrades collagen IV, a main component of the vascular basement membrane (BM), we subsequently investigated the effect of EIF5A2 on tumor vasculature remodeling using complementary approaches, including fluorescent immunostaining, transmission electron microscopy, tumor perfusion assays and tumor hypoxia assays. Taken together, our results indicate that EIF5A2 silencing increases tumor vessel wall continuity, increases blood perfusion and improves tumor oxygenation. Additionally, we found that ablation of EIF5A2 enhanced the chemosensitivity of HCC cells to 5-Fluorouracil (5-FU). Finally, we demonstrated that EIF5A2 might exert these functions by enhancing MMP-2 activity via activation of p38 MAPK and JNK/c-Jun pathways. Conclusion: This study highlights an important role of EIF5A2 in HCC tumor vessel remodeling and indicates that EIF5A2 represents a potential therapeutic target in the treatment of HCC.
Persistent Identifierhttp://hdl.handle.net/10722/210712
ISSN
2015 Impact Factor: 5.008
2015 SCImago Journal Rankings: 2.294
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWang, FW-
dc.contributor.authorCai, MY-
dc.contributor.authorMai, SJ-
dc.contributor.authorChen, JW-
dc.contributor.authorBai, HY-
dc.contributor.authorLi, Y-
dc.contributor.authorLiao, YJ-
dc.contributor.authorLi, CP-
dc.contributor.authorTian, XP-
dc.contributor.authorKung, HF-
dc.contributor.authorGuan, X-
dc.contributor.authorXie, D-
dc.date.accessioned2015-06-23T05:48:06Z-
dc.date.available2015-06-23T05:48:06Z-
dc.date.issued2014-
dc.identifier.citationOncotarget, 2014, v. 5 n. 16, p. 6716-6733-
dc.identifier.issn1949-2553-
dc.identifier.urihttp://hdl.handle.net/10722/210712-
dc.description.abstractHepatocellular carcinoma (HCC) is a highly vascularized tumor with poor clinical outcome. Our previous work has shown that eukaryotic initiation factor 5A2 (EIF5A2) over-expression enhances HCC cell metastasis. In this study, EIF5A2 was identified to be an independent risk factor for poor disease-specific survival among HCC patients. Both in vitro and in vivo assays indicated that ablation of endogenous EIF5A2 inhibited tumor angiogenesis by reducing matrix metalloproteinase 2 (MMP-2) expression. Given that MMP-2 degrades collagen IV, a main component of the vascular basement membrane (BM), we subsequently investigated the effect of EIF5A2 on tumor vasculature remodeling using complementary approaches, including fluorescent immunostaining, transmission electron microscopy, tumor perfusion assays and tumor hypoxia assays. Taken together, our results indicate that EIF5A2 silencing increases tumor vessel wall continuity, increases blood perfusion and improves tumor oxygenation. Additionally, we found that ablation of EIF5A2 enhanced the chemosensitivity of HCC cells to 5-Fluorouracil (5-FU). Finally, we demonstrated that EIF5A2 might exert these functions by enhancing MMP-2 activity via activation of p38 MAPK and JNK/c-Jun pathways. Conclusion: This study highlights an important role of EIF5A2 in HCC tumor vessel remodeling and indicates that EIF5A2 represents a potential therapeutic target in the treatment of HCC.-
dc.languageeng-
dc.publisherImpact Journals LLC. The Journal's web site is located at http://www.impactjournals.com/oncotarget/index.html-
dc.relation.ispartofOncotarget-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleAblation of EIF5A2 induces tumor vasculature remodeling and improves tumor response to chemotherapy via regulation of matrix metalloproteinase 2 expression-
dc.typeArticle-
dc.identifier.emailGuan, X: xyguan@hkucc.hku.hk-
dc.identifier.authorityGuan, X=rp00454-
dc.description.naturepublished_or_final_version-
dc.identifier.pmid25071013-
dc.identifier.pmcidPMC4196158-
dc.identifier.scopuseid_2-s2.0-84907084184-
dc.identifier.hkuros243536-
dc.identifier.volume5-
dc.identifier.issue16-
dc.identifier.spage6716-
dc.identifier.epage6733-
dc.identifier.isiWOS:000347920100018-
dc.publisher.placeUnited States-

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