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.

Details

Title
Caspase-8 deficiency induces a switch from TLR3 induced apoptosis to lysosomal cell death in neuroblastoma
Author
Marie-Anaïs, Locquet 1 ; Ichim Gabriel 2 ; Bisaccia, Joseph 1 ; Dutour Aurelie 1 ; Lebecque Serge 3 ; Castets Marie 1 ; Weber, Kathrin 1 

 Childhood Cancers and Cell Death Laboratory, Cancer Research Center of Lyon (CRCL), INSERM 1052, CNRS 5286, Lyon, France (GRID:grid.462282.8) (ISNI:0000 0004 0384 0005) 
 CRCL, Cancer Cell Death Laboratory, Part of LabEx DEVweCAN, Cancer Initiation and Tumoral Cell Identity Department, Lyon, France (GRID:grid.462282.8) (ISNI:0000 0004 0384 0005) 
 Childhood Cancers and Cell Death Laboratory, Cancer Research Center of Lyon (CRCL), INSERM 1052, CNRS 5286, Lyon, France (GRID:grid.462282.8) (ISNI:0000 0004 0384 0005); Service D’Anatomie Pathologique, Hospices Civils de Lyon, Hôpital Lyon Sud, Pierre-Bénite, France (GRID:grid.411430.3) (ISNI:0000 0001 0288 2594) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2529006847
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.