title: Activation of androgen receptor, lipogenesis, and oxidative stress converged by SREBP-1 is responsible for regulating growth and progression of prostate cancer cells.
abstract: 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 article, 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 (i) expression of SREBP-1 protein is positively associated with the clinical Gleason grades in human prostate cancer; (ii) 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 (iii) SREBP-1 induces and promotes the growth, migration, invasion, and castration-resistant progression of prostate cancer cells in vitro and in vivo. Our data show a novel molecular mechanism by which SREBP-1 promotes prostate cancer growth and progression through alterations in the concerted intracellular metabolic and signaling networks involving AR, lipogenesis, and ROS in prostate cancer cells.
authors: Uro-Oncology Research Program, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. wen-chin.huang@cshs.org
authors: Wen-Chin
authors: WC
authors: Huang
authors: Xiangyan
authors: X
authors: Li
authors: Jian
authors: J
authors: Liu
authors: Jentai
authors: J
authors: Lin
authors: Leland W K
authors: LW
authors: Chung
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D048708:Cell Growth Processes / Q000235:genetics*; D018450:Disease Progression; D006801:Humans; D050155:Lipogenesis / Q000235:genetics* / Q000502:physiology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D018384:Oxidative Stress / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism* / Q000502:physiology; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation / Q000235:genetics; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: C410798:AR protein, human; D017382:Reactive Oxygen Species; D011944:Receptors, Androgen; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1