17 beta-Estradiol via Orai1 activates calcium mobilization to induce cell proliferation in epithelial ovarian cancer
17 beta-Estradiol via Orai1 activates calcium mobilization to induce cell proliferation in epithelial ovarian cancer
复制标题
17 β-雌二醇通过 Orai1 激活钙动员，诱导上皮性卵巢癌细胞增殖
DOI：
10.1002/jbt.22603
复制
发表时间：
2020
影响因子：
3.6
通讯作者：
Wang Di
中科院分区：
文献类型：
--
作者：
Lv Xiaoyu;Miao Chunlei;Liu Mengyan;Wang Xinbo;Wang Lin;Wang Di
上皮性卵巢癌（EOC）是最致命的雌激素敏感性妇科癌症。研究已经报道，雌激素诱导细胞中的快速细胞钙动员，并且可以决定细胞的命运。我们发现雌激素增加了SK-OV-3细胞中钙释放激活的钙通道调节剂1（Orai 1）蛋白的表达水平。然而，迄今为止，还没有关于雌激素调节Orai 1在EOC发展中的功能关系和分子机制的研究。在我们的研究中，Orai 1在高级别浆液性卵巢肿瘤组织和SK‐OV‐3细胞中具有高表达水平。雌激素促进SK-OV-3细胞增殖和迁移，同时抑制细胞凋亡。Orai 1沉默抑制雌激素诱导的细胞迁移和增殖。然而，Orai 1的过表达增强了17β-雌二醇（E2）发挥其功能的能力。雌激素诱导SK-OV-3细胞快速钙内流。SK‐OV‐3细胞中Orai 1的敲低阻断了E2诱导的储存操作性Ca 2+内流。caspase 3、基质金属肽酶1和细胞周期蛋白依赖性激酶6的信使RNA表达在E2处理下通过Orai 1调节。我们的研究结果表明，雌激素，通过调节Orai 1，诱导钙内流，以确定细胞的命运。
Epithelial ovarian cancer (EOC) is the most lethal estrogen‐sensitive gynecological cancer. Studies have reported that estrogen induces rapid cellular calcium mobilization in cells and can determine the fate of a cell. We found that estrogen increased the calcium release‐activated calcium channel modulator 1 (Orai1) protein expression levels in SK‐OV‐3 cells. However, to date, there has been no research on the functional relationship and molecular mechanism of estrogen‐regulating Orai1 during EOC development. In our study, Orai1 had a high expression level in high‐grade serous ovarian tumor tissues and SK‐OV‐3 cells. Estrogen promoted cell proliferation and migration while inhibiting cell apoptosis in SK‐OV‐3 cells. Orai1 silencing suppressed estrogen‐induced cell migration and proliferation. Overexpression of Orai1, however, enhanced the ability of 17β‐estradiol (E2) to exert its function. Estrogen induced rapid calcium influx in SK‐OV‐3 cells. Knockdown of Orai1 in SK‐OV‐3 cells blocked E2‐induced stored‐operated Ca2+influx. The messenger RNA expression of caspase 3, matrix metallopeptidase 1, and cyclin‐dependent kinase 6 were regulated via Orai1 under E2 treatment. Our results suggest that estrogen, by regulating Orai1, induced calcium influx to determine cell fate.