Figure 5.

SphK1 and S1P signaling in colorectal carcinogenesis and progression. S1P produced by SphK1 results in the activation of NF-κB and IL-6/STAT3/AKT pathway intracellularly that prevents apoptosis, ultimately leading to cell transformation and angiogenesis in colitis-associated cancer and chronic intestinal inflammation, whereas signaling from S1PR1 maintains persistently activated STAT3 and up regulation of SphK, which contributes to the overall increase in S1P pool. Also, SphK inhibitors, SKI-II and FTY720 are known to suppress the progression of colon cancer.