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Oncotarget. 2017 Apr 18;8(16):27166-27176. doi: 10.18632/oncotarget.15677.

Sphingosine-1-phosphate promotes ovarian cancer cell proliferation by disrupting Hippo signaling.

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Department of Obstetrics and Gynaecology, British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, V5Z 4H4, Canada.
Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305-5317, USA.


Epithelial ovarian carcinomas account for more than 90% of human ovarian cancers and have become the primary cause of death for gynecological malignancies. Unlimited cell proliferation and resistance to cell apoptosis contribute to the development of ovarian cancers. However, the underlying mechanisms involved in these processes in epithelial ovarian carcinomas are yet poorly understood. In the present study, we examined the Hippo signaling gene expression and investigated the effects of Sphingosine 1-phosphate (S1P) on cell proliferation and the underlying mechanisms in human ovarian cancer cell lines, OVCAR3 and SKOV3. Our results demonstrate that S1P disrupts Hippo signaling by reducing YAP phosphorylation and increasing the expression of CCN1 and CCN2 in both ovarian cancer cells. Furthermore, the increase in CCN1/CCN2 expression contributes to the S1P-induced increase in cancer cell proliferation.


CCN1; CCN2; Hippo; YAP; ovarian cancer

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