Non-stem cell lineages as an alternative origin of intestinal tumorigenesis in the context of inflammation.
Nat Genet
; 56(7): 1456-1467, 2024 Jul.
Article
in En
| MEDLINE
| ID: mdl-38902475
ABSTRACT
According to conventional views, colon cancer originates from stem cells. However, inflammation, a key risk factor for colon cancer, has been shown to suppress intestinal stemness. Here, we used Paneth cells as a model to assess the capacity of differentiated lineages to trigger tumorigenesis in the context of inflammation in mice. Upon inflammation, Paneth cell-specific Apc mutations led to intestinal tumors reminiscent not only of those arising in patients with inflammatory bowel disease, but also of a larger fraction of human sporadic colon cancers. The latter is possibly because of the inflammatory consequences of western-style dietary habits, a major colon cancer risk factor. Machine learning methods designed to predict the cell-of-origin of cancer from patient-derived tumor samples confirmed that, in a substantial fraction of sporadic cases, the origins of colon cancer reside in secretory lineages and not in stem cells.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colonic Neoplasms
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Cell Lineage
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Paneth Cells
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Carcinogenesis
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Inflammation
Limits:
Animals
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Humans
Language:
En
Journal:
Nat Genet
Journal subject:
GENETICA MEDICA
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: