Bisphenol S Triggers the Migration and Invasion of Pheochromocytoma PC12 Cells via Estrogen-Related Receptor α.

Pheochromocytoma (PCC) is a tumor of the adrenal medulla for which surgical resection is the only therapy approach. Risk factors responsible for the tumorigenesis and progression of PCC are not well illustrated. Our present study revealed that an industrial chemical, bisphenol S (BPS), can promote the migration and invasion of PCC PC12 cells, which was evidenced by the upregulation of fibronectin (FN) and matrix metalloproteinases (MMP-2 and MMP-9). The inhibitor of estrogen-related receptor α (ERRα), while not estrogen receptor α/β (ERα/β) or G protein-coupled estrogen receptor (GPER), can attenuate BPS-induced cell migration. Mechanically, BPS can increase the binding between ERRα and promoter of FN1 and then induce the expression of FN in PC12 cells. Further, BPS can induce the expression of miR-10b in PC12 cells via ERRα. The upregulated miR-10b inhibited the expression of KLF4, which can suppress the migration and invasion of cancer cells. BPS can trigger the mRNA and protein expression of ERRα in PC12 cells via a time-dependent manner. Collectively, our study revealed that nanomolar BPS can trigger the migration and invasion of PC12 cells via activation and upregulation of ERRα.