Estrogen related receptor alpha triggers the migration and invasion of endometrial cancer cells via up regulation of TGFB1

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 (ERR alpha), while not ERR beta or ERR gamma, was significantly elevated in EC cells and tissues when compared to their controls. Targeted inhibition of ERR alpha by siRNA or its inverse agonist XCT-790 can suppress the migration and invasion of EC cells. Both si-ERR alpha and XCT-790 decreased the expression of transforming growth factor-beta (TGF-beta). ERR alpha can directly bind with the promoter of TGFB1 and then increase its transcription. Further, ERR alpha was involved in the positive self-feedback loop of TGF-beta in EC cells. Targeted inhibition of ERR alpha/TGF-beta can synergistically suppress the in vitro invasion of EC cells. Collectively, our data suggested that ERR alpha can trigger the cell migration and invasion via increasing the positive self-feedback regulation of TGF-beta.