2. Academic Validation
  3. Caspase-8 deficiency induces a switch from TLR3 induced apoptosis to lysosomal cell death in neuroblastoma

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

  • Sci Rep. 2021 May 19;11(1):10609. doi: 10.1038/s41598-021-89793-1.
Marie-Anaïs Locquet 1,  Gabriel Ichim 2,  Joseph Bisaccia 1,  Aurelie Dutour 1,  Serge Lebecque 1 3,  Marie Castets 4,  Kathrin Weber 5
Affiliations

Affiliations

  • 1 Childhood Cancers and Cell Death Laboratory, Cancer Research Center of Lyon (CRCL), INSERM 1052, CNRS 5286, Lyon, France.
  • 2 Cancer Cell Death Laboratory, Part of LabEx DEVweCAN, Cancer Initiation and Tumoral Cell Identity Department, CRCL, Lyon, France.
  • 3 Service D'Anatomie Pathologique, Hospices Civils de Lyon, Hôpital Lyon Sud, Pierre-Bénite, France.
  • 4 Childhood Cancers and Cell Death Laboratory, Cancer Research Center of Lyon (CRCL), INSERM 1052, CNRS 5286, Lyon, France. marie.castets@lyon.unicancer.fr.
  • 5 Childhood Cancers and Cell Death Laboratory, Cancer Research Center of Lyon (CRCL), INSERM 1052, CNRS 5286, Lyon, France. katrin.weber@lyon.unicancer.fr.
PMID: 34011952 DOI: 10.1038/s41598-021-89793-1
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.

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