雌激素相关受体 α 通过上调 TGFB1 触发子宫内膜癌细胞的迁移和侵袭。
Estrogen related receptor alpha triggers the migration and invasion of endometrial cancer cells via up regulation of TGFB1.
机构信息
a Department of Gynecology and Obstetrics , Zhongshan Hospital of Xiamen University , Xiamen , China.
b Organ Transplantation Institute, Xiamen University , No. 308, Xiang'an South Road, Xiamen City , Fujian Province , China.
出版信息
Cell Adh Migr. 2018;12(6):538-547. doi: 10.1080/19336918.2018.1477901. Epub 2018 Jun 25.
Estrogenic signals have been suggested to be important for the tumorigenesis and progression of endometrial cancer (EC) cells. Our present data showed that estrogen related receptor alpha (ERRα), while not ERRβ or ERRγ, was significantly elevated in EC cells and tissues when compared to their controls. Targeted inhibition of ERRα by siRNA or its inverse agonist XCT-790 can suppress the migration and invasion of EC cells. Both si-ERRα and XCT-790 decreased the expression of transforming growth factor-beta (TGF-β). ERRα can directly bind with the promoter of TGFB1 and then increase its transcription. Further, ERRα was involved in the positive self-feedback loop of TGF-β in EC cells. Targeted inhibition of ERRα/TGF-β can synergistically suppress the in vitro invasion of EC cells. Collectively, our data suggested that ERRα can trigger the cell migration and invasion via increasing the positive self-feedback regulation of TGF-β.
雌激素信号被认为对子宫内膜癌（EC）细胞的肿瘤发生和进展很重要。我们目前的数据显示，与对照相比，雌激素相关受体α（ERRα）而非 ERRβ或 ERRγ在 EC 细胞和组织中显著升高。siRNA 或其反向激动剂 XCT-790 靶向抑制 ERRα可抑制 EC 细胞的迁移和侵袭。si-ERRα 和 XCT-790 均降低转化生长因子-β（TGF-β）的表达。ERRα 可直接与 TGFB1 启动子结合，从而增加其转录。此外，ERRα参与了 EC 细胞中 TGF-β 的正自我反馈环。靶向抑制 ERRα/TGF-β 可协同抑制 EC 细胞的体外侵袭。总之，我们的数据表明，ERRα 可以通过增加 TGF-β 的正自我反馈调节来触发细胞迁移和侵袭。
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