Oxysterol receptors, AKT and prostate cancer
Oxysterol receptors, AKT and prostate cancer
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DOI：
10.1016/j.coph.2012.06.012
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发表时间：
2012-12-01
影响因子：
4
通讯作者：
Lobaccaro, Jean-Marc
中科院分区：
文献类型：
--
作者：
Dufour, Julie;Viennois, Emilie;Lobaccaro, Jean-Marc
氧化甾醇来源于胆固醇氧化。它们具有多种生物活性，如调节胆固醇、脂肪酸和葡萄糖的稳态以及细胞存活/凋亡平衡。氧化甾醇主要通过其核受体肝脏X受体(LXRs) α和β来显示这些代谢和转录活性。越来越多的证据表明LXRs是前列腺癌细胞存活的关键调节剂。因此，LXR激活增加胆固醇外排并诱导脂筏破坏。细胞膜胆固醇的降低导致AKT存活通路下调，进而导致细胞凋亡。此外，胆固醇与患侵袭性前列腺癌的风险增加有关。这些数据突出了LXR-AKT轴在前列腺癌发生中的作用。
Oxysterols derive from cholesterol oxidation. They display various biological activities such as regulating cholesterol, fatty acid and glucose homeostasis as well as cell survival/apoptosis balance. Oxysterols display these metabolic and transcriptional activities mainly through their nuclear receptors known as Liver X Receptors (LXRs) alpha and beta. There is accumulating evidence that LXRs are key modulators of prostate cancer cell survival. Hence, LXR activation increases cholesterol efflux and induces a disruption of lipid rafts. The decrease of membrane cholesterol causes a down regulation of AKT survival pathway and consequently apoptosis. Moreover cholesterol is associated with an increased risk of developing aggressive forms of prostate cancer. These data highlight the interest of targeting the LXR-AKT axis in prostate carcinogenesis.