SPHK1 and malignant colon neoplasm: The indication that COX-2 is under the control of SphK1 activity in colon cancer comes from the study showing that down-regulation of SphK1 in HT-29 human colon cancer cells reduces the expression of COX-2 and diminishes the generation of its enzymatic product prostaglandin E2 (PGE2), whereas over-expression of SphK1 in normal intestinal epithelial cells increases COX-2 expression [73].