UBE2L6/UBCH8 and ISG15 attenuate autophagy in esophageal cancer cells

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dc.contributor.authorFalvey, Chloe M.
dc.contributor.authorO'Donovan, Tracey R.
dc.contributor.authorEl-Mashad, Shereen M.
dc.contributor.authorNyhan, Michelle J.
dc.contributor.authorO'Reilly, Seamus
dc.contributor.authorMcKenna, Sharon L.
dc.contributor.funderUniversity College Corken
dc.contributor.funderHigher Education Authorityen
dc.contributor.funderBreakthrough Cancer Research, Ireland
dc.date.accessioned2017-03-09T12:45:05Z
dc.date.available2017-03-09T12:45:05Z
dc.date.issued2017-02-08
dc.date.updated2017-03-08T13:00:19Z
dc.description.abstractEsophageal 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.sponsorshipUniversity College Cork (Strategic Research Fund)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationFalvey, 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.15182en
dc.identifier.doi10.18632/oncotarget.15182
dc.identifier.endpage13en
dc.identifier.issn1949-2553
dc.identifier.journaltitleOncotargeten
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/3763
dc.language.isoenen
dc.publisherImpact Journalsen
dc.rights© 2017, the Authors. This article is licensed under a Creative Commons Attribution 3.0 License.en
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/en
dc.subjectEsophagealen
dc.subjectAutophagyen
dc.subjectApoptosisen
dc.subjectISG15en
dc.subjectUBE2L6en
dc.titleUBE2L6/UBCH8 and ISG15 attenuate autophagy in esophageal cancer cellsen
dc.typeArticle (peer-reviewed)en
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