Université Côte d'Azur, CNRS, INSERM, iBV, 06107 Nice, France.
Cells. 2020 May 4;9(5):1133. doi: 10.3390/cells9051133.
Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone receptor family. Three different isoforms, PPAR alpha, PPAR beta/delta and PPAR gamma have been identified. They all form heterodimers with retinoic X receptors to activate or repress downstream target genes dependent on the presence/absence of ligands and coactivators or corepressors. PPARs differ in their tissue expression profile, ligands and specific agonists and antagonists. PPARs attract attention as potential therapeutic targets for a variety of diseases. PPAR alpha and gamma agonists are in clinical use for the treatment of dyslipidemias and diabetes. For both receptors, several clinical trials as potential therapeutic targets for cancer are ongoing. In contrast, PPAR beta/delta has been suggested as a therapeutic target for metabolic syndrome. However, potential risks in the settings of cancer are less clear. A variety of studies have investigated PPAR beta/delta expression or activation/inhibition in different cancer cell models in vitro, but the relevance for cancer growth in vivo is less well documented and controversial. In this review, we summarize critically the knowledge of PPAR beta/delta functions for the different hallmarks of cancer biological capabilities, which interplay to determine cancer growth.
过氧化物酶体增殖物激活受体 (PPARs) 属于核激素受体家族。已经鉴定出三种不同的亚型，PPARα、PPARβ/δ 和 PPARγ。它们都与视黄酸 X 受体形成异二聚体，根据配体和共激活剂或核心抑制剂的存在/缺失来激活或抑制下游靶基因。PPARs 在其组织表达谱、配体和特定激动剂和拮抗剂方面存在差异。PPARs 作为各种疾病的潜在治疗靶点引起了关注。PPARα 和 PPARγ激动剂已用于治疗血脂异常和糖尿病。对于这两种受体，正在进行多项临床试验以评估其作为癌症的潜在治疗靶点的可能性。相比之下，PPARβ/δ 已被提议作为代谢综合征的治疗靶点。然而，在癌症环境下的潜在风险尚不清楚。各种研究已经在体外的不同癌症细胞模型中研究了 PPARβ/δ 的表达或激活/抑制，但在体内对癌症生长的相关性记录较少且存在争议。在这篇综述中，我们批判性地总结了 PPARβ/δ 功能在癌症生物学特性的不同标志中的知识，这些标志相互作用以确定癌症的生长。
