Thioredoxin interacting protein promotes invasion in hepatocellular carcinoma

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dc.contributor.authorGunes A.
dc.contributor.authorBagirsakci E.
dc.contributor.authorIscan E.
dc.contributor.authorCakan-Akdogan G.
dc.contributor.authorAykutlu U.
dc.contributor.authorSenturk S.
dc.contributor.authorOzhan G.
dc.contributor.authorErdal E.
dc.contributor.authorNart D.
dc.contributor.authorBarbet F.Y.
dc.contributor.authorAtabey N.
dc.date.accessioned2019-10-26T21:14:15Z
dc.date.available2019-10-26T21:14:15Z
dc.date.issued2018
dc.departmentEge Üniversitesien_US
dc.description.abstractBackground: Considerable evidence suggests that oxidative stress plays an essential role in the progression of hepatocellular carcinoma (HCC). While acquired resistance to oxidative stress is the main driver of aggressive cell phenotype, the underlying mechanisms remain unknown. Here, we tested the hypothesis that elevated expression of Thioredoxin-interacting protein (TXNIP) is a main regulator of the aggressive phenotype in HCC. Materials and Methods: To test this hypothesis, we measured TXNIP expression levels in 11 HCC cell lines by qPCR and western blotting. In addition, 80 pairs of HCC tissues and matched liver tissues of 73 cases, as well as 11 normal liver tissue samples were examined by immunohistochemistry. Besides, TXNIP expression levels were analyzed by Oncomine Platform in seven independent microarray datasets. Finally, the functional role of TXNIP in HCC was investigated in vitro and in vivo by silencing and overexpression studies. Results: Our results show that TXNIP expression is significantly increased in HCC compared to non-tumor counterparts (p < 0.0001) as well as to normal (p < 0.0001) and cirrhotic (p < 0.0001) liver tissues. Moreover, stable overexpression of TXNIP in HCC cells (i) significantly increases ROS levels, (ii) induces EMT phenotype, (iii) increases motility, invasion and 3D branching tubulogenesis, (iv) decreases apoptosis, and (v) elevates in vivo metastasis in zebrafish embryos. Finally, we identify sinusoidal/stromal and cytoplasmic TXNIP staining patterns as risk factors for intrahepatic vascular invasion (p:0.0400). Conclusion: Our results strongly suggest that overexpression of TXNIP has a pivotal role in HCC progression by inducing cell survival, invasion, and metastasis. Copyright: Gunes et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.description.sponsorship114S359en_US
dc.description.sponsorshipThis study was supported by The Scientific and Technological Research Council of Turkey (Project: 114S359). --en_US
dc.identifier.endpage36866en_US
dc.identifier.issn1949-2553
dc.identifier.issn1949-2553en_US
dc.identifier.issue96en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage36849en_US
dc.identifier.urihttps://hdl.handle.net/11454/15855
dc.identifier.volume9en_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherImpact Journals LLCen_US
dc.relation.ispartofOncotargeten_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectEMTen_US
dc.subjectHCCen_US
dc.subjectMetastasisen_US
dc.subjectOxidative stressen_US
dc.subjectTXNIPen_US
dc.titleThioredoxin interacting protein promotes invasion in hepatocellular carcinomaen_US
dc.typeArticleen_US

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