UBE2L6/UBCH8 and ISG15 attenuate autophagy in esophageal cancer cells

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dc.contributor.author Falvey, Chloe M.
dc.contributor.author O'Donovan, Tracey R.
dc.contributor.author El-Mashad, Shereen M.
dc.contributor.author Nyhan, Michelle J.
dc.contributor.author O'Reilly, Seamus
dc.contributor.author McKenna, Sharon L.
dc.date.accessioned 2017-03-09T12:45:05Z
dc.date.available 2017-03-09T12:45:05Z
dc.date.issued 2017-02-08
dc.identifier.citation Falvey, C. M., O’Donovan, T. R., El-Mashed, S., Nyhan, M. J., O’Reilly, S. and McKenna, S. L. (2017) 'UBE2L6/UBCH8 and ISG15 attenuate autophagy in esophageal cancer cells', Oncotarget, pp. 1-13. doi:10.18632/oncotarget.15182 en
dc.identifier.startpage 1 en
dc.identifier.endpage 13 en
dc.identifier.issn 1949-2553
dc.identifier.uri http://hdl.handle.net/10468/3763
dc.identifier.doi 10.18632/oncotarget.15182
dc.description.abstract Esophageal cancer remains a poor prognosis cancer due to advanced stage of presentation and drug resistant disease. To understand the molecular mechanisms influencing response to chemotherapy, we examined genes that are differentially expressed between drug sensitive, apoptosis competent esophageal cancer cells (OE21, OE33, FLO-1) and those which are more resistant and do not exhibit apoptosis (KYSE450 and OE19). Members of the ISG15 (ubiquitin-like) protein modification pathway, including UBE2L6 and ISG15, were found to be more highly expressed in the drug sensitive cell lines. In this study, we evaluated the contribution of these proteins to the response of drug sensitive cells. Depletion of UBE2L6 or ISG15 with siRNA did not influence caspase-3 activation or nuclear fragmentation following treatment with 5-fluorouracil (5-FU). We assessed autophagy by analysis of LC3II expression and Cyto-ID staining. Depletion of either ISG15 or UBE2L6 resulted in enhanced endogenous autophagic flux. An increase in autophagic flux was also observed following treatment with cytotoxic drugs (5-FU, rapamycin). In ISG15 depleted cells, this increase in autophagy was associated with improved recovery of drug treated cells. In contrast, UBE2L6 depleted cells, did not show enhanced recovery. UBE2L6 may therefore influence additional targets that limit the pro-survival effect of ISG15 depletion. These data identify UBE2L6 and ISG15 as novel inhibitors of autophagy, with the potential to influence chemosensitivity in esophageal cancer cells. en
dc.description.sponsorship University College Cork (Strategic Research Fund) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Impact Journals en
dc.rights © 2017, the Authors. This article is licensed under a Creative Commons Attribution 3.0 License. en
dc.rights.uri https://creativecommons.org/licenses/by/3.0/ en
dc.subject Esophageal en
dc.subject Autophagy en
dc.subject Apoptosis en
dc.subject ISG15 en
dc.subject UBE2L6 en
dc.title UBE2L6/UBCH8 and ISG15 attenuate autophagy in esophageal cancer cells en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Sharon McKenna, Surgery, University College Cork, Cork, Ireland. +353-21-490-3000 Email: s.mckenna@ucc.ie en
dc.internal.availability Full text available en
dc.date.updated 2017-03-08T13:00:19Z
dc.description.version Published Version en
dc.internal.rssid 386345423
dc.contributor.funder University College Cork en
dc.contributor.funder Higher Education Authority en
dc.contributor.funder Breakthrough Cancer Research, Ireland
dc.description.status Peer reviewed en
dc.identifier.journaltitle Oncotarget en
dc.internal.copyrightchecked Yes en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress s.mckenna@ucc.ie en

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© 2017, the Authors. This article is licensed under a Creative Commons Attribution 3.0 License. Except where otherwise noted, this item's license is described as © 2017, the Authors. This article is licensed under a Creative Commons Attribution 3.0 License.
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