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s41389-023-00450-w.pdf (2.53 MB)

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2023-02-08

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cc by (c) Favaro, Francesca et al., 2023
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/196615

Negligible role of TRAIL death receptors in cell death upon endoplasmic reticulum stress in B-cell malignancies

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https://doi.org/10.1038/s41389-023-00450-w

Resum

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.

Matèries

Limfomes, Apoptosi, Expressió gènica

Matèries (anglès)

Lymphomas, Apoptosis, Gene expression

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Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

FAVARO, Francesca, BOTH, Demi, DERKS, Ingrid a. m., SPAARGAREN, Marcel, MUÑOZ PINEDO, Cristina, ELDERING, Eric. Negligible role of TRAIL death receptors in cell death upon endoplasmic reticulum stress in B-cell malignancies. _Oncogenesis_. 2023. Vol. 12, núm. 1, pàgs. 6. [consulta: 28 de gener de 2026]. ISSN: 2157-9024. [Disponible a: https://hdl.handle.net/2445/196615]

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