| Autor: |
Francesca Favaro, Demi Both, Ingrid A. M. Derks, Marcel Spaargaren, Cristina Muñoz-Pinedo, Eric Eldering |
| Přispěvatelé: |
Experimental Immunology, Graduate School, AII - Cancer immunology, CCA - Cancer biology and immunology, Pathology |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Oncogenesis, 12(1):6. Nature Publishing Group |
| ISSN: |
2157-9024 |
| DOI: |
10.1038/s41389-023-00450-w |
| Popis: |
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, Waldenström’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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
|
Nepřihlášeným uživatelům se plný text nezobrazuje |
K zobrazení výsledku je třeba se přihlásit.
|
