The Role of Serum and Glucocorticoid-Regulated Kinase-1 (SGK1) in Prognosis and Therapy of Prostate Adenocarcinoma

Abstract

Prostate adenocarcinoma is an epithelial malignant neoplasm originating from the prostate, ranking as the second most common cancer in men. In Indonesia, around 50% of prostate adenocarcinoma cases are found to be metastatic. The condition of castrate-resistant prostate cancer (CRPC) that occurs during long-term administration of androgen deprivation therapy (ADT) has a significant impact on morbidity and mortality. Serum and glucocorticoid-regulated kinase-1 (SGK1) has been identified as having characteristics of a tumor-promoting gene. SGK1 expression is increased in several tumors, including prostate adenocarcinoma. SGK1 can be activated through several signaling pathways involved in prostate adenocarcinoma, including the phosphoinositide-3 kinase (PI3K) pathway, the androgen receptor (AR) pathway, and the glucocorticoid receptor (GR) pathway. SGK1 expression was found to be positively correlated with progression and metastasis of prostate adenocarcinoma. This shows that SGK1 can be a positive predictor of prostate adenocarcinoma metastasis. The significant relationship between high SGK1 expression and the occurrence of CRPC indicates that SGK1 can act as a prognostic biomarker for prostate adenocarcinoma which can develop into CRPC. Specific inhibitors of SGK1 significantly interfere with the migration and invasion of prostate adenocarcinoma cells through silencing SGK1 which causes G2/M cycle arrest, activation of apoptosis and autophagy in prostate adenocarcinoma cells.