Importantly, this study found that induced ERK1/2 was able to enhance PKD-mediated SphK2 activation and its consequent translocation to the cytoplasm to further negatively regulate NaBT-induced apoptosis in colon cancer cells, and provided an evidence to demonstrate that activation of ERK1/2 is an upstream event that precedes the induction of PKD and SphK2 in response to NaBT [106]. This evidence concerns the gene MAPK3 and colonic neoplasm.