脂筏
肝X受体
生物
LNCaP公司
细胞生物学
下调和上调
信号转导
蛋白激酶B
细胞凋亡
甾醇调节元件结合蛋白
胆固醇
内分泌学
内科学
癌症研究
癌细胞
甾醇
核受体
生物化学
癌症
转录因子
医学
基因
遗传学
作者
Aurélien Pommier,Georges Alves,Émilie Viennois,Sophie Bernard,Y Communal,Benoı̂t Sion,Geoffroy Marceau,Coralie Damon,Kévin Mouzat,Françoise Caira,S Baron,Jean‐Marc Lobaccaro
出处
期刊:Oncogene
[Springer Nature]
日期:2010-03-01
卷期号:29 (18): 2712-2723
被引量:174
摘要
Cholesterol is a structural component of lipid rafts within the plasma membrane. These domains, used as platforms for various signaling molecules, regulate cellular processes including cell survival. Cholesterol contents are tightly correlated with the structure and function of lipid rafts. Liver X receptors (LXRs) have a central role in the regulation of cholesterol homeostasis within the cell. Therefore, we investigated whether these nuclear receptors could modulate lipid raft signaling and consequently alter prostate cancer (PCa) cell survival. Treatment with the synthetic LXR agonist T0901317 downregulated the AKT survival pathway and thus induced apoptosis of LNCaP PCa cells in both xenografted nude mice and cell culture. The decrease in tumor cholesterol content resulted from the upregulation of ABCG1 and the subsequent increase in reverse cholesterol transport. RNA interference experiments showed that these effects were mediated by LXRs. Atomic force microscopy scanning of the inner plasma membrane sheet showed smaller and thinner lipid rafts after LXR stimulation, associated with the downregulation of AKT phosphorylation in these lipid rafts. Replenishment of cell membranes with exogenous cholesterol antagonized these effects, showing that cholesterol is a key modulator in this process. Altogether, pharmacological modulation of LXR activity could thus reduce prostate tumor growth by enhancing apoptosis in a lipid raft-dependent manner.
科研通智能强力驱动
Strongly Powered by AbleSci AI