Knockdown of sterol O-acyltransferase 1 (SOAT1) suppresses SCD1-mediated lipogenesis and cancer procession in prostate cancer.

Prostate cancer (PCa) is one of the most fatal malignant tumors that occurs in the prostate epithelium, especially in older men, the mortality of which ranks sixth among all cancer-related deaths. It has been urgently needed to elucidate the pathogenesis of PCa and provide promising therapeutic targets for PCa treatment. The Sterol O-acyltransferase 1 (SOAT1), cholesterol metabolism enzyme, was widely expressed in various cancer tissues, resulting in cancer progression. SOAT1 has been demonstrated to be highly expressed in prostate cancer tissues, whereas the underlying mechanism has not been elucidated. Herein, we found the expression of SOAT1 was elevated in human PCa tissues, which demonstrated SOAT1 level was correlated with lymph node metastasis (p = 0.006), clinical stage (p = 0.032), grading (p = 0.036), and Gleason score (p = 0.030) of PCa patients. In addition, we revealed that SOAT1 promoted proliferation and liposynthesis of PCa cells by targeting Stearoyl-CoA Desaturase 1 (SCD1). Our data further confirmed that SCD1 overexpression reversed the proliferation and liposynthesis defects caused by SOAT1 depletion in PCa cells, however, SOAT1 depletion inhibited tumor growth of PCa cells in mice. We further found SOAT1 contributed to the progression of PCa via SREBF1 pathway. Taken together, our data revealed the mechanism underlying SOAT1 promoting PCa progression in vitro and in vivo.