Activation of SphK1 by adipocytes mediates epithelial ovarian cancer cell proliferation

Abstract

Abstract Background Adipocytes, active facilitators of epithelial ovarian cancer (EOC) growth, have been implicated in the link between obesity and EOC. However, the current understanding of the mechanisms underlying adipocyte-induced EOC cell proliferation remains incomplete. Results We provide the first evidence showing that sphingosine kinase (SphK) 1 is critical for adipocyte-induced EOC cell proliferation. Adipocytes are capable of activating SphK1, which then leads to extracellular signal-regulated kinase (ERK) phosphorylation. Moreover, adipocyte-induced SphK1 activation is ERK dependent. Furthermore, sphingosine 1-phosphate receptor (S1PR) 1 and S1PR3, key components of the SphK1 signalling pathway, participate in adipocyte-mediated growth-promoting action in EOC cells. Conclusions Our study reveals a previously unrecognized role of SphK1 in adipocyte-induced growth-promoting action in EOC, suggesting a new target for EOC therapy.

Keywords

• Epithelial ovarian cancer (EOC)
• Adipocytes
• Sphingosine kinase 1 (SphK1)
• Sphingosine 1-phosphate receptor (S1PR)
• Proliferation