Epithelial NAIPs protect against colonic tumorigenesis.

Allam, Ramanjaneyulu; Maillard, Michel H; Tardivel, Aubry; Chennupati, Vijaykumar; Bega, Hristina; Yu, Chi Wang; Velin, Dominique; Schneider, Pascal; Maslowski, Kendle M (2015). Epithelial NAIPs protect against colonic tumorigenesis. The Journal of experimental medicine, 212(3), pp. 369-383. Rockefeller Univ. Press 10.1084/jem.20140474

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Hämatologie (Erwachsene)

UniBE Contributor:

Allam, Ramanjaneyulu

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1540-9538

Publisher:

Rockefeller Univ. Press

Language:

English

Submitter:

Verena Zwahlen

Date Deposited:

17 Mar 2015 14:50

Last Modified:

09 Sep 2017 22:32

Publisher DOI:

10.1084/jem.20140474

PubMed ID:

25732303

Uncontrolled Keywords:

Epithelial NAIPs

BORIS DOI:

10.7892/boris.64631

URI:

https://boris.unibe.ch/id/eprint/64631

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