However, genetic deletion of Sphk1 reduced AOM/DSS-induced development of chronic colitis and intestinal tumor formation in the mice [46], leading to the downregulation of NF-κB and production of NF-κB-regulated proinflammatory cytokines tumor necrosis factorα (TNF-α) and Interleukin 6 (IL-6), and signal transducer and activator of transcription 3 (Stat3), which are key mediators in colitis and in the development of colitis-associated colorectal cancer (CAC) [47,48]. Here, TNF is linked to colitis.