SPHK1 and cancer: In stark contrast, the biosynthesis of S1P that is driven by SPHKs, particularly SPHK1, appears to exert pro-survival and anti-apoptotic effects in cancer cells, by promoting cancer cell proliferation, therapy resistance, tumor invasion and metastasis via S1P receptor (S1PR)-dependent and/or -independent signaling pathways (Hannun and Obeid, 2018; Ogretmen, 2018).