SPHK2 and breast cancer: HDACs are negative regulators of the ERα transcriptional complex and HDAC inhibitors have been shown to epigenetically restore ERα expression and reverse TAM resistance in hormone-resistant breast cancer cells6, 7, 31, 32 and in preclinical animal studies.33, 34 As we found that FTY720 is phosphorylated in the nucleus of ERα-negative MDA-MB-231 and 4T1 breast cancer cells by SphK2 (Figure 1) and that FTY720-P is a potent class I HDAC inhibitor, we asked whether it induces ERα re-expression in ERα-negative breast cancer.