Sphingosine-1-phosphate promotes ovarian cancer cell proliferation by disrupting Hippo signaling.
Sphingosine-1-phosphate promotes ovarian cancer cell proliferation by disrupting Hippo signaling.
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DOI：
10.18632/oncotarget.15677
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发表时间：
2017-04-18
期刊：
影响因子：
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通讯作者：
Leung PCK
中科院分区：
文献类型：
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作者：
Fan Q;Cheng Y;Chang HM;Deguchi M;Hsueh AJ;Leung PCK
上皮性卵巢癌占人类卵巢癌的90%以上，已成为妇科恶性肿瘤的主要死亡原因。无限制的细胞增殖和对细胞凋亡的抵抗有助于卵巢癌的发展。然而，上皮性卵巢癌中这些过程的潜在机制还知之甚少。在本研究中，我们检测了Hippo信号基因的表达，并研究了1-磷酸鞘氨醇（S1 P）对人卵巢癌细胞系OVCAR 3和SKOV 3细胞增殖的影响及其潜在机制。我们的研究结果表明，S1 P通过减少雅普磷酸化和增加两种卵巢癌细胞中CCN 1和CCN 2的表达来破坏Hippo信号传导。此外，CCN 1/CCN 2表达的增加有助于S1 P诱导的癌细胞增殖的增加。
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.