Laboratory of Mathematics and Applications, Unités Mixtes de Recherche (UMR), Centre National de la Recherche Scientifique (CNRS) 7348, University of Poitiers, Poitiers, France.
Délégation à la Recherche Clinique et à l'Innovation (DRCI), Hôpital Foch, Suresnes, France.
Neurosci Bull. 2018 Jun;34(3):573-588. doi: 10.1007/s12264-018-0219-5. Epub 2018 Mar 26.
In gliomas, the canonical Wingless/Int (WNT)/β-catenin pathway is increased while peroxisome proliferator-activated receptor gamma (PPAR-γ) is downregulated. The two systems act in an opposite manner. This review focuses on the interplay between WNT/β-catenin signaling and PPAR-γ and their metabolic implications as potential therapeutic target in gliomas. Activation of the WNT/β-catenin pathway stimulates the transcription of genes involved in proliferation, invasion, nucleotide synthesis, tumor growth, and angiogenesis. Activation of PPAR-γ agonists inhibits various signaling pathways such as the JAK/STAT, WNT/β-catenin, and PI3K/Akt pathways, which reduces tumor growth, cell proliferation, cell invasiveness, and angiogenesis. Nonsteroidal anti-inflammatory drugs, curcumin, antipsychotic drugs, adiponectin, and sulforaphane downregulate the WNT/β-catenin pathway through the upregulation of PPAR-γ and thus appear to provide an interesting therapeutic approach for gliomas. Temozolomide (TMZ) is an antiangiogenic agent. The downstream action of this opposite interplay may explain the TMZ-resistance often reported in gliomas.
在神经胶质瘤中，经典的 Wingless/Int（WNT）/β-连环蛋白途径增加，而过氧化物酶体增殖物激活受体γ（PPAR-γ）下调。这两个系统以相反的方式起作用。这篇综述重点介绍了 WNT/β-连环蛋白信号通路与 PPAR-γ 之间的相互作用及其作为神经胶质瘤潜在治疗靶点的代谢意义。WNT/β-连环蛋白途径的激活刺激参与增殖、侵袭、核苷酸合成、肿瘤生长和血管生成的基因的转录。PPAR-γ 激动剂的激活抑制各种信号通路，如 JAK/STAT、WNT/β-连环蛋白和 PI3K/Akt 通路，从而减少肿瘤生长、细胞增殖、细胞侵袭和血管生成。非甾体抗炎药、姜黄素、抗精神病药、脂联素和萝卜硫素通过上调 PPAR-γ 下调 WNT/β-连环蛋白途径，因此似乎为神经胶质瘤提供了一种有趣的治疗方法。替莫唑胺（TMZ）是一种抗血管生成剂。这种相反相互作用的下游作用可能解释了神经胶质瘤中经常报道的 TMZ 耐药性。
