Epithelial memory of inflammation limits tissue damage while promoting pancreatic tumorigenesis.
Science
; 373(6561): eabj0486, 2021 Sep 17.
Article
em En
| MEDLINE
| ID: mdl-34529467
ABSTRACT
Inflammation is a major risk factor for pancreatic ductal adenocarcinoma (PDAC). When occurring in the context of pancreatitis, KRAS mutations accelerate tumor development in mouse models. We report that long after its complete resolution, a transient inflammatory event primes pancreatic epithelial cells to subsequent transformation by oncogenic KRAS. Upon recovery from acute inflammation, pancreatic epithelial cells display an enduring adaptive response associated with sustained transcriptional and epigenetic reprogramming. Such adaptation enables the reactivation of acinar-to-ductal metaplasia (ADM) upon subsequent inflammatory events, thereby limiting tissue damage through a rapid decrease of zymogen production. We propose that because activating mutations of KRAS maintain an irreversible ADM, they may be beneficial and under strong positive selection in the context of recurrent pancreatitis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pâncreas
/
Pancreatite
/
Genes ras
/
Carcinoma Ductal Pancreático
/
Células Acinares
/
Carcinogênese
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Science
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos