Clermont Université, Université Blaise Pascal, Génétique Reproduction et Développement F-63000 CLERMONTFERRAND, France ; CNRS, UMR 6293, GReD F-63177 AUBIERE, France ; INSERM, UMR 1103, GReD F-63177 AUBIERE, France ; Centre de Recherche en Nutrition Humaine d'Auvergne F-63000 CLERMONT-FERRAND, France.
Am J Cancer Res. 2013;3(1):58-69. Epub 2013 Jan 18.
Cholesterol is a fundamental molecule for life. Located in the cell membrane, this sterol participates to the cell signaling of growth factors. Inside the cell it can be converted in hormones such as androgens or modulate the immune response. Such important functions could not be solely dependent of external supply by diet hence de novo synthesis could occur from acetate in almost all mammalian cells. If a deficiency in cholesterol sourcing leads to development troubles, overstocking has been associated to various diseases such as atherosclerosis and cancers. Cholesterol homeostasis should thus be tightly regulated at the uptake, de novo synthesis, storage and export processes. Various transcription factors have been described these last years as important to regulate cholesterol levels. Besides, synthetic molecules have been developed for many years to modulate cholesterol synthesis, such as statins. Many articles have associated prostate cancer, whose incidence is constantly increasing, to cholesterol disequilibrium. Targeting cholesterol could thus be a new pharmacological hit to counteract the initiation, development and/or progression of prostate cancer. Among the transcription factors regulating cholesterol homeostasis, the nuclear receptors Liver X Receptors (LXRs) control cholesterol uptake and export. Targeting the LXRs offers a new field of investigation to treat cancer. This review highlights the molecular relationships among LXRs, prostate cancer and cholesterol and why LXRs have good chance to be targeted one day in this tumor. LXRs, prostate cancer and cholesterol, more than a "Ménage à trois", The Good, the Bad and the Ugly.
胆固醇是生命的基本分子。这种固醇位于细胞膜中，参与生长因子的细胞信号转导。在细胞内，它可以转化为雄激素等激素，或调节免疫反应。如此重要的功能不可能仅仅依赖于饮食的外部供应，因此几乎所有哺乳动物细胞都可以从乙酸盐从头合成胆固醇。如果胆固醇来源的缺乏导致发育问题，那么过量储存与各种疾病有关，如动脉粥样硬化和癌症。因此，胆固醇的动态平衡应该在摄取、从头合成、储存和输出过程中受到严格调节。近年来，已经描述了多种转录因子对调节胆固醇水平很重要。此外，多年来已经开发出许多合成分子来调节胆固醇合成，如他汀类药物。许多文章将不断增加的前列腺癌的发病率与胆固醇失衡联系起来。因此，靶向胆固醇可能是一种新的药理学方法，可以抑制前列腺癌的起始、发展和/或进展。在调节胆固醇动态平衡的转录因子中，核受体肝 X 受体 (LXRs) 控制胆固醇的摄取和输出。靶向 LXRs 为治疗癌症提供了一个新的研究领域。这篇综述强调了 LXRs、前列腺癌和胆固醇之间的分子关系，以及为什么 LXRs 有一天很有可能成为该肿瘤的靶向目标。LXRs、前列腺癌和胆固醇，不仅仅是“三人行”，好的、坏的和丑陋的。
