LDL, HDL and endocrine-related cancer: From pathogenic mechanisms to therapies

胆固醇 内分泌系统 内科学 内分泌学 癌症 肝X受体 癌症研究 前列腺癌 清道夫受体 生物 医学 脂蛋白 激素 核受体 生物化学 基因 转录因子
作者
Giovanna Revilla,Lídia Cedó,Mireia Tondo,Antonio Moral,José Ignacio Arias Pérez,Rosa Corcoy,Enrique Lerma,Victòria Fusté,Srivinasa T. Reddy,Francisco Blanco‐Vaca,Eugènia Mato,Joan Carles Escolà‐Gil
出处
期刊:Seminars in Cancer Biology [Elsevier BV]
卷期号:73: 134-157 被引量:50
标识
DOI:10.1016/j.semcancer.2020.11.012
摘要

Cholesterol is essential for a variety of functions in endocrine-related cells, including hormone and steroid production. We have reviewed the progress to date in research on the role of the main cholesterol-containing lipoproteins; low-density lipoprotein (LDL) and high-density lipoprotein (HDL), and their impact on intracellular cholesterol homeostasis and carcinogenic pathways in endocrine-related cancers. Neither LDL-cholesterol (LDL-C) nor HDL-cholesterol (HDL-C) was consistently associated with endocrine-related cancer risk. However, preclinical studies showed that LDL receptor plays a critical role in endocrine-related tumor cells, mainly by enhancing circulating LDL-C uptake and modulating tumorigenic signaling pathways. Although scavenger receptor type BI-mediated uptake of HDL could enhance cell proliferation in breast, prostate, and ovarian cancer, these effects may be counteracted by the antioxidant and anti-inflammatory properties of HDL. Moreover, 27-hydroxycholesterol a metabolite of cholesterol promotes tumorigenic processes in breast and epithelial thyroid cancer. Furthermore, statins have been reported to reduce the incidence of breast, prostate, pancreatic, and ovarian cancer in large clinical trials, in part because of their ability to lower cholesterol synthesis. Overall, cholesterol homeostasis deregulation in endocrine-related cancers offers new therapeutic opportunities, but more mechanistic studies are needed to translate the preclinical findings into clinical therapies.
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