Necroptosis is dispensable for the development of inflammation-associated or sporadic colon cancer in mice.
Journal
Cell death and differentiation
ISSN: 1476-5403
Titre abrégé: Cell Death Differ
Pays: England
ID NLM: 9437445
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
17
04
2020
accepted:
04
11
2020
revised:
04
11
2020
pubmed:
25
11
2020
medline:
24
2
2022
entrez:
24
11
2020
Statut:
ppublish
Résumé
Chronic inflammation of the large intestine is associated with an increased risk of developing colorectal cancer (CRC), the second most common cause of cancer-related deaths worldwide. Necroptosis has emerged as a form of lytic programmed cell death that, distinct from apoptosis, triggers an inflammatory response. Dysregulation of necroptosis has been linked to multiple chronic inflammatory diseases, including inflammatory bowel disease and cancer. Here, we used murine models of acute colitis, colitis-associated CRC, sporadic CRC, and spontaneous intestinal tumorigenesis to investigate the role of necroptosis in these gastrointestinal pathologies. In the Dextran Sodium Sulfate-induced acute colitis model, in some experiments, mice lacking the terminal necroptosis effector protein, MLKL, or its activator RIPK3, exhibited greater weight loss compared to wild-type mice, consistent with some earlier reports. However, the magnitude of weight loss and accompanying inflammatory pathology upon Mlkl deletion varied substantially between independent repeats. Such variation provides a possible explanation for conflicting literature reports. Furthermore, contrary to earlier reports, we observed that genetic deletion of MLKL had no impact on colon cancer development using several mouse models. Collectively, these data do not support an obligate role for necroptosis in inflammation or cancer within the gastrointestinal tract.
Identifiants
pubmed: 33230260
doi: 10.1038/s41418-020-00673-z
pii: 10.1038/s41418-020-00673-z
pmc: PMC8167101
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1466-1476Subventions
Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : 1172929
Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : 1124735
Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : 1124737
Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : 1113577
Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : 1058344
Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : 461221
Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : 1116937
Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : 1113133
Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : 1143105
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