Epithelial NAIPs protect against colonic tumorigenesis.
Détails
Etat: Public
Version: Final published version
ID Serval
serval:BIB_B4563C30990A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Epithelial NAIPs protect against colonic tumorigenesis.
Périodique
Journal of Experimental Medicine
ISSN
1540-9538 (Electronic)
ISSN-L
0022-1007
Statut éditorial
Publié
Date de publication
2015
Volume
212
Numéro
3
Pages
369-383
Langue
anglais
Résumé
NLR family apoptosis inhibitory proteins (NAIPs) belong to both the Nod-like receptor (NLR) and the inhibitor of apoptosis (IAP) families. NAIPs are known to form an inflammasome with NLRC4, but other in vivo functions remain unexplored. Using mice deficient for all NAIP paralogs (Naip1-6(Δ/Δ)), we show that NAIPs are key regulators of colorectal tumorigenesis. Naip1-6(Δ/Δ) mice developed increased colorectal tumors, in an epithelial-intrinsic manner, in a model of colitis-associated cancer. Increased tumorigenesis, however, was not driven by an exacerbated inflammatory response. Instead, Naip1-6(Δ/Δ) mice were protected from severe colitis and displayed increased antiapoptotic and proliferation-related gene expression. Naip1-6(Δ/Δ) mice also displayed increased tumorigenesis in an inflammation-independent model of colorectal cancer. Moreover, Naip1-6(Δ/Δ) mice, but not Nlrc4-null mice, displayed hyper-activation of STAT3 and failed to activate p53 18 h after carcinogen exposure. This suggests that NAIPs protect against tumor initiation in the colon by promoting the removal of carcinogen-elicited epithelium, likely in a NLRC4 inflammasome-independent manner. Collectively, we demonstrate a novel epithelial-intrinsic function of NAIPs in protecting the colonic epithelium against tumorigenesis.
Pubmed
Web of science
Open Access
Oui
Création de la notice
10/04/2015 19:19
Dernière modification de la notice
20/08/2019 16:22