Dai Lan, Wang Chen, Wang Wenjing, Song Keqi, Ye Taiyang, Zhu Jie, Di Wen
Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
Department of Cell Biology, Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
Open Med (Wars). 2022 Jan 31;17(1):229-238. doi: 10.1515/med-2022-0422. eCollection 2022.
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.
上皮性卵巢癌（EOC）是女性癌症死亡的主要原因。脂肪细胞被认为在刺激EOC生长中起关键作用。然而，脂肪细胞诱导EOC增殖的潜在机制仍不明确。在此，我们提供了首个证据，即脂肪细胞可诱导EOC中鞘氨醇激酶（SphK）2的激活，这代表了一条介导脂肪细胞诱导EOC生长的新途径。EOC细胞中SphK2的抑制导致脂肪细胞诱导的细胞增殖显著受到抑制。此外，EOC细胞中脂肪细胞诱导的SphK2激活依赖于细胞外信号调节蛋白激酶（ERK）。此外，EOC中SphK2的沉默显著抑制了脂肪细胞诱导的磷酸化ERK和c-Myc的表达，这两者是EOC生长中的两个关键因子。总的来说，当前研究揭示了SphK2在脂肪细胞诱导的EOC生长促进作用中一个此前未被认识到的作用，提示了EOC治疗的一个新靶点。
