Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/28398
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dc.contributor.authorPaul, I.-
dc.contributor.authorChacko, A.D.-
dc.contributor.authorStasik, I.-
dc.contributor.authorBusacca, S.-
dc.contributor.authorCrawford, N.-
dc.contributor.authorMcCoy, F.-
dc.contributor.authorMcTavish, N.-
dc.contributor.authorWilson, B.-
dc.contributor.authorBarr, M.-
dc.contributor.authorO'Byrne, K.J.-
dc.contributor.authorLongley, D.B.-
dc.contributor.authorFennell, Dean A.-
dc.date.accessioned2013-11-14T13:14:06Z-
dc.date.available2013-11-14T13:14:06Z-
dc.date.issued2012-09-21-
dc.identifier.citationCell Death and Disease, 2012, 3, e449en
dc.identifier.urihttp://www.nature.com/cddis/journal/v3/n12/full/cddis2012186a.htmlen
dc.identifier.urihttp://hdl.handle.net/2381/28398-
dc.descriptionPMCID: PMC3542622en
dc.description.abstractFailure to efficiently induce apoptosis contributes to cisplatin resistance in non-small-cell lung cancer (NSCLC). Although BCL-2-associated X protein (BAX) and BCL-2 antagonist killer (BAK) are critical regulators of the mitochondrial apoptosis pathway, their requirement has not been robustly established in relation to cisplatin. Here, we show that cisplatin can efficiently bypass mitochondrial apoptosis block caused by loss of BAX and BAK, via activation of the extrinsic death receptor pathway in some model cell lines. Apoptosis resistance following cisplatin can only be observed when both extrinsic and intrinsic pathways are blocked, consistent with redundancy between mitochondrial and death receptor pathways in cisplatin-induced apoptosis. In H460 NSCLC cells, caspase-8 cleavage was shown to be induced by cisplatin and is dependent on death receptor 4, death receptor 5, Fas-associated protein with death domain, acid sphingomyelinase and ceramide synthesis. In contrast, cisplatin-resistant cells fail to activate caspase-8 via this pathway despite conserving sensitivity to death ligand-driven activation. Accordingly, caspase-8 activation block acquired during cisplatin resistance, can be bypassed by death receptor agonism.en
dc.language.isoenen
dc.publisherNature Publishing Group for Associazione Differenziamento e Morte Cellulareen
dc.relation.urihttp://www.ncbi.nlm.nih.gov/pubmed/23254292-
dc.rightsCopyright © 2012, Nature Publishing Group. This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/.en
dc.subjectApoptosisen
dc.subjectCarcinoma, Non-Small-Cell Lungen
dc.subjectCaspase 8en
dc.subjectCell Line, Tumoren
dc.subjectCisplatinen
dc.subjectDrug Resistance, Neoplasmen
dc.subjectGene Expression Regulation, Enzymologicen
dc.subjectGene Expression Regulation, Neoplasticen
dc.subjectHumansen
dc.subjectLung Neoplasmsen
dc.subjectProtein Processing, Post-Translationalen
dc.titleAcquired differential regulation of caspase-8 in cisplatin-resistant non-small-cell lung cancer.en
dc.typeJournal Articleen
dc.identifier.doi10.1038/cddis.2012.186-
dc.identifier.eissn2041-4889-
dc.identifier.piicddis2012186-
dc.description.statusPeer-revieweden
dc.description.versionPublisher Versionen
dc.type.subtypeJournal Article;Research Support, Non-U.S. Gov't-
pubs.organisational-group/Organisationen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGYen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicineen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Cancer Studies and Molecular Medicineen
Appears in Collections:Published Articles, Dept. of Cancer Studies and Molecular Medicine

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