SPHK1 and breast carcinoma: Although SPHKs are predominantly cytosolic enzymes (45), both SPHK1 and SPHK2 (46, 47) can be abundantly expressed in the nucleus of cancer cell lines such as MCF7, COS7, and HeLa cells and a higher nuclear expression of SPHK1 has been associated with significantly shorter survival in breast cancer patients (44).