Acquired differential regulation of caspase-8 in cisplatin-resistant non-small-cell lung cancer

Failure 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 estab...

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Main Authors:	Paul, I, Chacko, A D, Stasik, I, Busacca, S, Crawford, N, McCoy, F, McTavish, N, Wilson, B, Barr, M, O'Byrne, K J, Longley, D B, Fennell, D A
Format:	Online
Language:	English
Published:	Nature Publishing Group 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3542622/

id	pubmed-3542622
recordtype	oai_dc
spelling	pubmed-35426222013-01-11 Acquired differential regulation of caspase-8 in cisplatin-resistant non-small-cell lung cancer Paul, I Chacko, A D Stasik, I Busacca, S Crawford, N McCoy, F McTavish, N Wilson, B Barr, M O'Byrne, K J Longley, D B Fennell, D A Original Article Failure 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. Nature Publishing Group 2012-12 2012-12-20 /pmc/articles/PMC3542622/ /pubmed/23254292 http://dx.doi.org/10.1038/cddis.2012.186 Text en Copyright © 2012 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ 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/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Paul, I Chacko, A D Stasik, I Busacca, S Crawford, N McCoy, F McTavish, N Wilson, B Barr, M O'Byrne, K J Longley, D B Fennell, D A
spellingShingle	Paul, I Chacko, A D Stasik, I Busacca, S Crawford, N McCoy, F McTavish, N Wilson, B Barr, M O'Byrne, K J Longley, D B Fennell, D A Acquired differential regulation of caspase-8 in cisplatin-resistant non-small-cell lung cancer
author_facet	Paul, I Chacko, A D Stasik, I Busacca, S Crawford, N McCoy, F McTavish, N Wilson, B Barr, M O'Byrne, K J Longley, D B Fennell, D A
author_sort	Paul, I
title	Acquired differential regulation of caspase-8 in cisplatin-resistant non-small-cell lung cancer
title_short	Acquired differential regulation of caspase-8 in cisplatin-resistant non-small-cell lung cancer
title_full	Acquired differential regulation of caspase-8 in cisplatin-resistant non-small-cell lung cancer
title_fullStr	Acquired differential regulation of caspase-8 in cisplatin-resistant non-small-cell lung cancer
title_full_unstemmed	Acquired differential regulation of caspase-8 in cisplatin-resistant non-small-cell lung cancer
title_sort	acquired differential regulation of caspase-8 in cisplatin-resistant non-small-cell lung cancer
description	Failure 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.
publisher	Nature Publishing Group
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3542622/
_version_	1611946236733030400

Acquired differential regulation of caspase-8 in cisplatin-resistant non-small-cell lung cancer

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