In many ways, cancer can be seen as the end stage of chronic inflammation, but the steps in this transition are still being delineated. Kanneganti and colleagues, in Cancer Cell, provide evidence that NLRP12, a member of the Nod-like receptor family of proteins, has a pivotal role in regulating inflammation and tumorigenesis in the gut. Published studies have suggested that NLRP12 may have an anti-inflammatory function, but the data on this have been conflicting. To address this, the authors generate Nlrp12−/− mice and find that they are hypersusceptible to both chemically induced colitis and tumorigenesis in the colon. In these conditions, Nlrp12−/− mice are also characterized by more inflammation and infiltration of the colon by granulocytes and T cells. Colon samples from Nlrp12−/− mice and Nlrp12−/− macrophages in vitro also show dysregulated signaling via the transcription factor NF-κB, mitogen-activated kinases and cytokines. Studies of bone marrow chimeras indicate that NLRP12 is important mainly in the hematopoietic compartment. NLRP12 therefore has a critical role in restraining inflammation and tumorigenesis.

Cancer Cell 20, 649–660 (2011)