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...

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Autores principales:	Marie-Anaïs Locquet, Gabriel Ichim, Joseph Bisaccia, Aurelie Dutour, Serge Lebecque, Marie Castets, Kathrin Weber
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/02c2b7516d5647c2ac6cdfa292b56d48
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spelling	oai:doaj.org-article:02c2b7516d5647c2ac6cdfa292b56d482021-12-02T15:45:31ZCaspase-8 deficiency induces a switch from TLR3 induced apoptosis to lysosomal cell death in neuroblastoma10.1038/s41598-021-89793-12045-2322https://doaj.org/article/02c2b7516d5647c2ac6cdfa292b56d482021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89793-1https://doaj.org/toc/2045-2322Abstract 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.Marie-Anaïs LocquetGabriel IchimJoseph BisacciaAurelie DutourSerge LebecqueMarie CastetsKathrin WeberNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
author	Marie-Anaïs Locquet Gabriel Ichim Joseph Bisaccia Aurelie Dutour Serge Lebecque Marie Castets Kathrin Weber
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 Portfolio
publishDate	2021
url	https://doaj.org/article/02c2b7516d5647c2ac6cdfa292b56d48
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Caspase-8 deficiency induces a switch from TLR3 induced apoptosis to lysosomal cell death in neuroblastoma

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