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http://hdl.handle.net/2445/196615
Title: | Negligible role of TRAIL death receptors in cell death upon endoplasmic reticulum stress in B-cell malignancies |
Author: | Favaro, Francesca Both, Demi Derks, Ingrid A. M. Spaargaren, Marcel Muñoz Pinedo, Cristina Eldering, Eric |
Keywords: | Limfomes Apoptosi Expressió gènica Lymphomas Apoptosis Gene expression |
Issue Date: | 8-Feb-2023 |
Publisher: | Springer Science and Business Media LLC |
Abstract: | Impairments in protein folding in the endoplasmic reticulum (ER) lead to a condition called ER stress, which can trigger apoptosis via the mitochondrial or the death receptor (extrinsic) pathway. There is controversy concerning involvement of the death receptor (DR)4 and DR5-Caspase-8 -Bid pathway in ER stress-mediated cell death, and this axis has not been fully studied in B-cell malignancies. Using three B-cell lines from Mantle Cell Lymphoma, Waldenstrom's macroglobulinemia and Multiple Myeloma origins, we engineered a set of CRISPR KOs of key components of these cell death pathways to address this controversy. We demonstrate that DR4 and/or DR5 are essential for killing via TRAIL, however, they were dispensable for ER-stress induced-cell death, by Thapsigargin, Brefeldin A or Bortezomib, as were Caspase-8 and Bid. In contrast, the deficiency of Bax and Bak fully protected from ER stressors. Caspase-8 and Bid were cleaved upon ER-stress stimulation, but this was DR4/5 independent and rather a result of mitochondrial-induced feedback loop subsequent to Bax/Bak activation. Finally, combined activation of the ER-stress and TRAIL cell-death pathways was synergistic with putative clinical relevance for B-cell malignancies. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s41389-023-00450-w |
It is part of: | Oncogenesis, 2023, vol. 12, num. 1, p. 6 |
URI: | http://hdl.handle.net/2445/196615 |
Related resource: | https://doi.org/10.1038/s41389-023-00450-w |
ISSN: | 2157-9024 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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File | Description | Size | Format | |
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s41389-023-00450-w.pdf | 2.59 MB | Adobe PDF | View/Open |
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