Activation of SphK2 contributes to adipocyte-induced EOC cell proliferation

Epithelial ovarian cancer (EOC) is the leading cause of deaths due to cancer in women. Adipocytes have been suggested to play a key role in the stimulation of EOC growth. However, the mechanisms underlying the adipocyte-induced EOC proliferation remain undefined. Here, we provide the first evidence that adipocytes induce the activation of sphingosine kinase (SphK) 2 in EOC, which represents a novel pathway that mediates the adipocyte-induced EOC growth. SphK2 inhibition in EOC cells led to a remarkable inhibition of the adipocyte-induced cell proliferation. Moreover, the adipocyte-induced SphK2 activation in EOC cells was extracellular signal-regulated protein kinases (ERK) dependent. Furthermore, silencing SphK2 in EOC significantly inhibited the adipocyte-induced expression of phospho-ERK and c-Myc, two crucial players in EOC growth. Collectively, the current study unraveled a previously unrecognized role of SphK2 in the adipocyte-induced growth-promoting action in EOC, suggesting a novel target for EOC treatment.

Automated summary

This study reveals the involvement of adipocytes in promoting the growth of epithelial ovarian cancer (EOC) and identifies sphingosine kinase 2 (SphK2) as a key mediator in this process. Inhibition of SphK2 significantly suppresses adipocyte-induced EOC cell proliferation, which is dependent on the activation of extracellular signal-regulated protein kinases (ERK). Furthermore, silencing SphK2 inhibits the adipocyte-induced expression of phospho-ERK and c-Myc, two crucial factors in EOC growth.