Activation of Androgen Receptor, Lipogenesis, and Oxidative Stress Converged by SREBP-1 is Responsible for Regulating Growth and Progression of Prostate Cancer Cells

Overview

Journal Mol Cancer Res

Specialty Cell Biology

Date 2011 Nov 9

PMID 22064655

Citations 129

Authors

Wen-Chin Huang

Xiangyan Li

Jian Liu

Jentai Lin

Leland W K Chung

Affiliations

Soon will be listed here.

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.

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