肝X受体α:胆固醇转运和癌症调控的共同平台

Liver X receptorα:the common platform for cholesterol transport and cancer regulation

胆固醇是维持细胞结构所必需的基本分子,对各种正常的生物功能至关重要,其代谢异常可能增加肥胖、心血管疾病的风险,也与癌症的发生、发展密切相关。肝X受体(LXR)α属于核受体家族成员之一,可促进胆固醇排泄、参与胆固醇逆转运,降低胆固醇水平,是维持胆固醇正常转运的重要因子。LXRα在肝癌、乳腺癌、结直肠癌、肺癌等多种癌症中存在异常表达。LXRα可靶向三磷酸腺苷结合盒转运体蛋白(ABC)A1、3-羟基-3-甲基戊二酰辅酶A还原酶(HMGCR)、胆固醇调节元件结合蛋白1(SREBP1)和过氧化物酶体增殖物激活受体α(PPARα)等多种下游基因,既在胆固醇转运,又在癌症调控中发挥关键作用。本文就近年来LXRα在胆固醇转运及癌症调控方面的研究进展进行综述,以期为癌症防治提供新的思路。

Cholesterol is a fundamental molecule necessary to maintain cell structure and crucial for various normal biological functions.Its metabolic abnormalities increase the risk of obesity and cardiovascular disease,and might be closely related to the occurrence and development of cancer.Liver X receptor(LXR)α,as a member of the nuclear receptor family,can promote cholesterol excretion,participate in reverse cholesterol transport,and lower cholesterol levels.It is an important factor in maintaining normal cholesterol transport.LXRαexpression is abnormal in liver cancer,breast cancer,colorectal cancer,lung cancer and other cancers.And LXRαcan target and regulate the expression of various downstream genes,such as ATP binding cassette transporter(ABC)A1,3-hydroxy-3-methylglutaryl coenzyme A reductase(HMGCR),sterol-regulatory element binding protein 1(SREBP1),and peroxisome proliferator-activated receptorα(PPARα).It plays a key role for LXRαin both cholesterol transport and regulating cancer.This article reviews the research progress of LXRαin cholesterol transport and cancer regulation,in order to provide new ideas for cancer prevention and treatment.