Serum- and Glucocorticoid-inducible Kinase 1 is Essential for Osteoclastogenesis and Promotes Breast Cancer Bone Metastasis

Abstract

Bone metastasis is a severe complication associated with various carcinomas. It causes debilitating pain and pathologic fractures and dramatically impairs patients' quality of life. Drugs aimed at osteoclast formation significantly reduce the incidence of skeletal complications and are currently the standard treatment for patients with bone metastases. Here, we reported that serum- and glucocorticoid-inducible kinase 1 (SGK1) plays a pivotal role in the formation and function of osteoclasts by regulating the Ca²⁺ release-activated Ca²⁺ channel Orai1. We showed that SGK1 inhibition represses osteoclastogenesis <i>in vitro</i> and prevents bone loss <i>in vivo</i> Furthermore, we validated the effect of SGK1 on bone metastasis by using an intracardiac injection model in mice. Inhibition of SGK1 resulted in a significant reduction in bone metastasis. Subsequently, the Oncomine and the OncoLnc database were employed to verify the differential expression and the association with clinical outcome of <i>SGK1</i> gene in patients with breast cancer. Our data mechanistically demonstrated the regulation of the SGK1 in the process of osteoclastogenesis and revealed SGK1 as a valuable target for curing bone metastasis diseases.