STAT3 and sphingosine-1-phosphate in inflammation-associated colorectal cancer

Accumulated evidences have demonstrated that signal transducer and activator of transcription 3 (STAT3) is a critical link between inflammation and cancer. Multiple studies have indicated that persistent activation of STAT3 in epithelial/tumor cells in inflammation-associated colorectal cancer (CRC) is associated with sphingosine-1-phosphate (S1P) receptor signaling. In inflammatory response whereby interleukin (IL)-6 production is abundant, STAT3-mediated pathways were found to promote the activation of sphingosine kinases (SphK1 and SphK2) leading to the production of S1P. Reciprocally, S1P encourages the activation of STAT3 through a positive autocrine-loop signaling. The crosstalk between IL-6, STAT3 and sphingolipid regulated pathways may play an essential role in tumorigenesis and tumor progression in inflamed intestines. Therapeutics targeting both STAT3 and sphingolipid are therefore likely to contribute novel and more effective therapeutic strategies against inflammation-associated CRC. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.