Estrogen-Related Receptor Promotes The Migration And Metastasis Of Endometrial Cancer Cells By Targeting S100a4

S100 calcium binding protein A4 (S100A4) is a well-established tumor metastasis mediator in various malignancies, including endometrial cancer (EC). However, the regulatory mechanism underlying S100A4 expression remains elusive. In the present study, by analyzing public datasets and clinical samples, we found that estrogen-related receptor (ERR) was upregulated and positively correlated with S100A4 transcription in EC. ERR knockdown inhibited S100A4 expression and promoted the expression of its downstream target E-cadherin, and vice versa. Mechanistic studies indicated that ERR enhanced the promoter activity of S100A4 to facilitate its transcription. In addition, knockdown of ERR suppressed migration and invasion of EC cells in vitro, while ectopic ERR expression promoted migration and invasion of EC cells in vitro and tumor growth in vivo. Importantly, restoration of S100A4 expression prevented EC cells from undergoing ERR-mediated changes in these biological features. In addition, synchronous changes in S100A4 and ERR expression were observed after incubation with estrogen. Overall, ERR may exert oncogenic activity mainly associated with aggressiveness of EC by activating S100A4 transcription and thus may be a novel therapeutic target in EC.