Sphingosine kinase 1 contributes to the metastatic potential of epithelial ovarian cancer to the adipocyte-rich niche

Unlike many solid tumors, epithelial ovarian cancer (EOC) has a clear metastatic predilection to the adipocyte-rich niche, especially the omentum. However, the underlying mechanism driving this process remains incomplete. Here we show that SphK1 is over-expressed in omental metastases compared with ovarian primary tumors in EOC patients. In vitro, inhibition of SphK1 suppressed the metastatic ability of EOC induced by adipocytes. In vivo, blockage of SphK1 could attenuate the omental metastasis of EOC. Importantly, SphK1 modulates adipocyte-induced E/N-cadherin switch through Twist1, a key process in EOC metastasis. Our study reveals a previously unrecognized role of SphK1 in modulating the metastatic tropism of EOC to the adipocyte-rich niche, suggesting a new target for EOC therapy.