Laboratoire de Biochimie Générale et Appliquée, UFR de Pharmacie, MMS-EA 2160-Mer Molécules Santé, IUML-Institut Universitaire Mer et Littoral-FR3473 CNRS, Université de Nantes, 44035 Nantes, France.
Institut de Cancérologie de l'Ouest, Boulevard Jacques Monod, 44805 Saint-Herblain CEDEX, France.
Int J Mol Sci. 2020 Feb 17;21(4):1356. doi: 10.3390/ijms21041356.
Breast cancer is the most frequent cancer among women. In 2018, it is estimated that 627,000 women died from breast cancer. This is approximately 15% of all cancer deaths among women (WHO 2018). Breast cancer is a multifactorial chronic disease. While important progress has been made to treat patients, many questions regarding aspects of this disease relating to carcinogenesis are still open. During carcinogenesis, cells exhibit cholesterol homeostasis deregulation. This results in an accumulation of intracellular cholesterol, which is required to sustain their high growth rate. Cholesterol efflux and influx are two metabolic pathways that are necessary to prevent cholesterol accumulation in the cells. Liver X receptors (LXRs) are nuclear receptors that, upon activation, induce the expression of ABC transporters, responsible for promoting cholesterol efflux, and the expression of IDOL (inducible degrader of low-density lipoprotein receptor), in charge of reducing cholesterol influx. Oxysterols, oxygenated derivatives of cholesterol formed through different pathways, have been discovered as LXR-specific ligands. Some oxysterols are involved in tumor formation while others are considered anti-tumor agents. In the present review, we discuss the involvement of cholesterol, oxysterols and LXRs in breast cancer pathophysiology, with an emphasis on the biological effects of LXR ligands.
乳腺癌是女性中最常见的癌症。据估计，2018 年有 62.7 万名女性死于乳腺癌，约占女性癌症死亡总数的 15%（世界卫生组织，2018 年）。乳腺癌是一种多因素的慢性疾病。尽管在治疗患者方面取得了重要进展，但与癌症发生相关的许多方面仍存在问题。在癌变过程中，细胞表现出胆固醇稳态失调。这导致细胞内胆固醇积累，而胆固醇是维持其高生长速度所必需的。胆固醇外排和内流是两种必需的代谢途径，可防止胆固醇在细胞内积累。肝 X 受体（LXRs）是核受体，激活后诱导 ABC 转运蛋白的表达，负责促进胆固醇外排，以及 IDOL（低密度脂蛋白受体降解诱导物）的表达，负责减少胆固醇内流。通过不同途径形成的胆固醇的氧化衍生物——氧化固醇，已被发现是 LXR 的特异性配体。一些氧化固醇参与肿瘤形成，而另一些则被认为是抗肿瘤剂。在本次综述中，我们讨论了胆固醇、氧化固醇和 LXRs 在乳腺癌病理生理学中的作用，重点介绍了 LXR 配体的生物学效应。
