1 Activation of androgen receptor, lipogenesis and oxidative stress converged by SREBP-1 is responsible for regulating growth and progression of prostate cancer cells

2 We previously reported that sterol regulatory element-binding protein-1 (SREBP-1) is involved in the transcriptional regulation of androgen receptor (AR) and formation of fatty acid through altered expression of fatty acid synthase (FASN). In this communication, we provide a new finding that SREBP-1 induced oxidative stress in prostate cancer cells through increased production of reactive oxygen species (ROS) and expression of NADPH oxidase 5 (Nox5). We have shown that: 1) Expression of SREBP-1 protein is positively associated with the clinical Gleason grades in human prostate cancer; 2) Genetic overexpression or knockdown of SREBP-1 in prostate cancer cells resulted in corresponding increased or decreased AR, FASN and Nox5 expression, fatty acid and lipid droplet accumulation, and ROS generation; and 3) SREBP-1 induces and promotes the growth, migration, invasion and castration-resistant progression of prostate cancer cells in vitro and in vivo. Our data demonstrate a novel molecular mechanism by which SREBP-1 promotes prostate cancer growth and progression through alterations in th