SPHK1 and malignant colon neoplasm: Alternatively, overexpression of SphK1 and aberrations in the “inside-out” dual mechanism of SphK1/S1P activation have been reported as contributors to cancer and inflammation [38, 39, 56, 78, 79], and this is supported by studies in SphK1-deficient mice, for example, reduction of SphK1 reduced colon cancer development [80, 81].