CNRS, INSERM, iBV, Université Côte d'Azur, 06107 Nice, France.
Cells. 2022 Aug 5;11(15):2432. doi: 10.3390/cells11152432.
Peroxisome proliferator-activated receptors (PPARs) function as nuclear transcription factors upon the binding of physiological or pharmacological ligands and heterodimerization with retinoic X receptors. Physiological ligands include fatty acids and fatty-acid-derived compounds with low specificity for the different PPAR subtypes (alpha, beta/delta, and gamma). For each of the PPAR subtypes, specific pharmacological agonists and antagonists, as well as pan-agonists, are available. In agreement with their natural ligands, PPARs are mainly focused on as targets for the treatment of metabolic syndrome and its associated complications. Nevertheless, many publications are available that implicate PPARs in malignancies. In several instances, they are controversial for very similar models. Thus, to better predict the potential use of PPAR modulators for personalized medicine in therapies against malignancies, it seems necessary and timely to review the three PPARs in relation to the didactic concept of cancer hallmark capabilities. We previously described the functions of PPAR beta/delta with respect to the cancer hallmarks and reviewed the implications of all PPARs in angiogenesis. Thus, the current review updates our knowledge on PPAR beta and the hallmarks of cancer and extends the concept to PPAR alpha and PPAR gamma.
过氧化物酶体增殖物激活受体（PPARs）在与视黄酸 X 受体（RXR）形成异二聚体并结合生理或药理配体后，作为核转录因子发挥作用。生理配体包括具有低特异性的脂肪酸和脂肪酸衍生化合物，用于不同的 PPAR 亚型（α、β/δ和γ）。对于每种 PPAR 亚型，都有特定的药理学激动剂和拮抗剂，以及泛激动剂。与它们的天然配体一致，PPAR 主要被认为是治疗代谢综合征及其相关并发症的靶点。然而，有许多出版物表明 PPAR 与恶性肿瘤有关。在许多情况下，对于非常相似的模型，它们存在争议。因此，为了更好地预测 PPAR 调节剂在针对恶性肿瘤的个性化医学治疗中的潜在用途，似乎有必要及时地根据癌症标志性特征的教学概念来审查三种 PPAR。我们之前描述了 PPARβ/δ 与癌症标志性特征的关系，并回顾了所有 PPAR 在血管生成中的作用。因此，本综述更新了我们对 PPARβ 和癌症标志性特征的认识，并将这一概念扩展到了 PPARα 和 PPARγ。
