Molecular Pathways: Dietary Regulation of Stemness and Tumor Initiation by the PPAR-δ Pathway.
Molecular Pathways: Dietary Regulation of Stemness and Tumor Initiation by the PPAR-δ Pathway.
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DOI：
10.1158/1078-0432.ccr-16-0775
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发表时间：
2016-12-01
期刊：
影响因子：
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通讯作者：
Yilmaz ÖH
中科院分区：
文献类型：
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作者：
Beyaz S;Yilmaz ÖH
过氧化物酶体激活受体δ（过氧化物酶体激活受体-δ）是一种核受体转录因子，在发育和疾病状态如癌症期间调节基因表达。然而，PPAR-δ在肿瘤发生过程中的确切作用还不清楚。最近的数据表明，PPAR-δ可能具有背景特异性致癌和肿瘤抑制作用，这取决于组织，细胞类型或饮食诱导的生理学问题。例如，在肠道中，促肥胖饮食，如高脂肪饮食（HFD），与结肠直肠癌发病率增加有关。有趣的是，HFD在干细胞和祖细胞区室中的许多作用是由强大的PPAR-δ程序驱动的，并有助于肠道肿瘤发生的早期步骤。重要的是，PPAR-δ通路或其下游介质可以作为结肠癌的治疗干预点或生物标志物，特别是在肥胖患者中出现。尽管存在有效的PPAR-δ激动剂和拮抗剂，但通过揭示PPAR-δ如何介导不同组织和细胞类型中的肿瘤发生以及对饮食的反应，可以增强其临床应用。
Peroxisome Proliferator-Activated Receptor delta (PPAR-δ) is a nuclear receptor transcription factor that regulates gene expression during development and disease states such as cancer. However, the precise role of PPAR-δ during tumorigenesis is not well understood. Recent data suggest that PPAR-δ may have context specific oncogenic and tumor suppressive roles depending on the tissue, cell-type, or diet-induced physiology in question. For example in the intestine, pro-obesity diets, like a high fat diet (HFD), are associated with increased colorectal cancer incidence. Interestingly, many of the effects of a HFD in the stem and progenitor cell compartment are driven by a robust PPAR-δ program and contribute to the early steps of intestinal tumorigenesis. Importantly, the PPAR-δ pathway or its downstream mediators may serve as therapeutic intervention points or biomarkers in colon cancer that particularly arise in obese patients. Although potent PPAR-δ agonists and antagonists exist, their clinical utility may be enhanced by uncovering how PPAR-δ mediates tumorigenesis in diverse tissues and cell-types as well as in response to diet.