Caspase-8 deficiency induces a switch from TLR3 induced apoptosis to lysosomal cell death in neuroblastoma

Abstract In cancer cells only, TLR3 acquires death receptor properties by efficiently triggering the extrinsic pathway of apoptosis with Caspase-8 as apical protease. Here, we demonstrate that in the absence of Caspase-8, activation of TLR3 can trigger a form of programmed cell death, which is disti...

Full description

Bibliographic Details
Main Authors:	Marie-Anaïs Locquet, Gabriel Ichim, Joseph Bisaccia, Aurelie Dutour, Serge Lebecque, Marie Castets, Kathrin Weber
Format:	Article
Language:	English
Published:	Nature Publishing Group 2021-05-01
Series:	Scientific Reports
Online Access:	https://doi.org/10.1038/s41598-021-89793-1

id	doaj-02c2b7516d5647c2ac6cdfa292b56d48
record_format	Article
spelling	doaj-02c2b7516d5647c2ac6cdfa292b56d482021-05-23T11:31:39ZengNature Publishing GroupScientific Reports2045-23222021-05-011111910.1038/s41598-021-89793-1Caspase-8 deficiency induces a switch from TLR3 induced apoptosis to lysosomal cell death in neuroblastomaMarie-Anaïs Locquet0Gabriel Ichim1Joseph Bisaccia2Aurelie Dutour3Serge Lebecque4Marie Castets5Kathrin Weber6Childhood Cancers and Cell Death Laboratory, Cancer Research Center of Lyon (CRCL), INSERM 1052, CNRS 5286Cancer Cell Death Laboratory, Part of LabEx DEVweCAN, Cancer Initiation and Tumoral Cell Identity Department, CRCLChildhood Cancers and Cell Death Laboratory, Cancer Research Center of Lyon (CRCL), INSERM 1052, CNRS 5286Childhood Cancers and Cell Death Laboratory, Cancer Research Center of Lyon (CRCL), INSERM 1052, CNRS 5286Childhood Cancers and Cell Death Laboratory, Cancer Research Center of Lyon (CRCL), INSERM 1052, CNRS 5286Childhood Cancers and Cell Death Laboratory, Cancer Research Center of Lyon (CRCL), INSERM 1052, CNRS 5286Childhood Cancers and Cell Death Laboratory, Cancer Research Center of Lyon (CRCL), INSERM 1052, CNRS 5286Abstract In cancer cells only, TLR3 acquires death receptor properties by efficiently triggering the extrinsic pathway of apoptosis with Caspase-8 as apical protease. Here, we demonstrate that in the absence of Caspase-8, activation of TLR3 can trigger a form of programmed cell death, which is distinct from classical apoptosis. When TLR3 was activated in the Caspase-8 negative neuroblastoma cell line SH-SY5Y, cell death was accompanied by lysosomal permeabilization. Despite caspases being activated, lysosomal permeabilization as well as cell death were not affected by blocking caspase-activity, positioning lysosomal membrane permeabilization (LMP) upstream of caspase activation. Taken together, our data suggest that LMP with its deadly consequences represents a “default” death mechanism in cancer cells, when Caspase-8 is absent and apoptosis cannot be induced.https://doi.org/10.1038/s41598-021-89793-1
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Marie-Anaïs Locquet Gabriel Ichim Joseph Bisaccia Aurelie Dutour Serge Lebecque Marie Castets Kathrin Weber
spellingShingle	Marie-Anaïs Locquet Gabriel Ichim Joseph Bisaccia Aurelie Dutour Serge Lebecque Marie Castets Kathrin Weber Caspase-8 deficiency induces a switch from TLR3 induced apoptosis to lysosomal cell death in neuroblastoma Scientific Reports
author_facet	Marie-Anaïs Locquet Gabriel Ichim Joseph Bisaccia Aurelie Dutour Serge Lebecque Marie Castets Kathrin Weber
author_sort	Marie-Anaïs Locquet
title	Caspase-8 deficiency induces a switch from TLR3 induced apoptosis to lysosomal cell death in neuroblastoma
title_short	Caspase-8 deficiency induces a switch from TLR3 induced apoptosis to lysosomal cell death in neuroblastoma
title_full	Caspase-8 deficiency induces a switch from TLR3 induced apoptosis to lysosomal cell death in neuroblastoma
title_fullStr	Caspase-8 deficiency induces a switch from TLR3 induced apoptosis to lysosomal cell death in neuroblastoma
title_full_unstemmed	Caspase-8 deficiency induces a switch from TLR3 induced apoptosis to lysosomal cell death in neuroblastoma
title_sort	caspase-8 deficiency induces a switch from tlr3 induced apoptosis to lysosomal cell death in neuroblastoma
publisher	Nature Publishing Group
series	Scientific Reports
issn	2045-2322
publishDate	2021-05-01
description	Abstract In cancer cells only, TLR3 acquires death receptor properties by efficiently triggering the extrinsic pathway of apoptosis with Caspase-8 as apical protease. Here, we demonstrate that in the absence of Caspase-8, activation of TLR3 can trigger a form of programmed cell death, which is distinct from classical apoptosis. When TLR3 was activated in the Caspase-8 negative neuroblastoma cell line SH-SY5Y, cell death was accompanied by lysosomal permeabilization. Despite caspases being activated, lysosomal permeabilization as well as cell death were not affected by blocking caspase-activity, positioning lysosomal membrane permeabilization (LMP) upstream of caspase activation. Taken together, our data suggest that LMP with its deadly consequences represents a “default” death mechanism in cancer cells, when Caspase-8 is absent and apoptosis cannot be induced.
url	https://doi.org/10.1038/s41598-021-89793-1
work_keys_str_mv	AT marieanaislocquet caspase8deficiencyinducesaswitchfromtlr3inducedapoptosistolysosomalcelldeathinneuroblastoma AT gabrielichim caspase8deficiencyinducesaswitchfromtlr3inducedapoptosistolysosomalcelldeathinneuroblastoma AT josephbisaccia caspase8deficiencyinducesaswitchfromtlr3inducedapoptosistolysosomalcelldeathinneuroblastoma AT aureliedutour caspase8deficiencyinducesaswitchfromtlr3inducedapoptosistolysosomalcelldeathinneuroblastoma AT sergelebecque caspase8deficiencyinducesaswitchfromtlr3inducedapoptosistolysosomalcelldeathinneuroblastoma AT mariecastets caspase8deficiencyinducesaswitchfromtlr3inducedapoptosistolysosomalcelldeathinneuroblastoma AT kathrinweber caspase8deficiencyinducesaswitchfromtlr3inducedapoptosistolysosomalcelldeathinneuroblastoma
_version_	1721429531449884672

Caspase-8 deficiency induces a switch from TLR3 induced apoptosis to lysosomal cell death in neuroblastoma

Similar Items