The Role of Cholesterol in Cancer.
The Role of Cholesterol in Cancer.
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DOI：
10.1158/0008-5472.can-15-2613
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发表时间：
2016-04-15
期刊：
影响因子：
11.2
通讯作者：
Robertson GP
中科院分区：
文献类型：
--
作者：
Kuzu OF;Noory MA;Robertson GP
胆固醇在癌症发展中所起的作用以及治疗靶向胆固醇稳态的潜力在癌症界是一个有争议的领域。几项流行病学研究报告了癌症与血清胆固醇水平或他汀类药物使用之间的关联，而其他研究则表明没有关联。此外，使用下一代测序的癌症基因组图谱（TCGA）项目已经分析了不同癌症中所有基因的突变状态和表达水平，包括参与胆固醇代谢的基因，为胆固醇途径在癌症发展中的作用提供了相关支持。最后，临床前研究倾向于更一致地支持胆固醇在癌症中的作用，其中一些研究表明胆固醇稳态基因可以调节发育。由于篇幅的限制，本次审查提供了选定的流行病学，TCGA和临床前数据的例子，重点是胆固醇稳态的改变及其对患者生存的影响。在黑色素瘤中，这项集中的分析表明，胆固醇合成基因的表达增强与患者生存率降低有关。总的来说，黑色素瘤和其他癌症类型的研究表明，胆固醇稳态破坏在癌症发展中的潜在作用，但需要额外的研究来联系基于人群的流行病学数据，TCGA数据库结果和临床前机制证据，以具体解决这一争议。
The roles played by cholesterol in cancer development and the potential of therapeutically targeting cholesterol homeostasis is a controversial area in the cancer community. Several epidemiological studies report an association between cancer and serum cholesterol levels or statin use, while others suggest that there is not one. Furthermore, the Cancer Genome Atlas (TCGA) project using next-generation sequencing has profiled the mutational status and expression levels of all the genes in diverse cancers, including those involved in cholesterol metabolism, providing correlative support for a role of the cholesterol pathway in cancer development. Finally, preclinical studies tend to more consistently support a role of cholesterol in cancer with several demonstrating that cholesterol homeostasis genes can modulate development. Due to space limitations, this review provides selected examples of the epidemiological, TCGA and preclinical data, focusing on alterations in cholesterol homeostasis and its consequent effect on patient survival. In melanoma, this focused analysis, demonstrated that enhanced expression of cholesterol synthesis genes was associated with decreased patient survival. Collectively, the studies in melanoma and other cancer types, suggested a potential role of disrupted cholesterol homeostasis in cancer development but that additional studies are needed to link population based epidemiological data, the TCGA database results and preclinical mechanistic evidence to concretely resolve this controversy.