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Opposite Interplay Between the Canonical WNT/β-Catenin Pathway and PPAR Gamma: A Potential Therapeutic Target in Gliomas

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Abstract

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.

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Authors and Affiliations

  1. Laboratory of Mathematics and Applications, Unités Mixtes de Recherche (UMR), Centre National de la Recherche Scientifique (CNRS) 7348, University of Poitiers, Poitiers, France

    Alexandre Vallée & Jean-Noël Vallée

  2. Délégation à la Recherche Clinique et à l’Innovation (DRCI), Hôpital Foch, Suresnes, France

    Alexandre Vallée

  3. Centre de Recherche Clinique, Grand Hôpital de l’Est Francilien, Meaux, France

    Yves Lecarpentier

  4. DACTIM, UMR CNRS 7348, University of Poitiers et CHU de Poitiers, Poitiers, France

    Rémy Guillevin

  5. CHU Amiens Picardie, University of Picardie Jules Verne, Amiens, France

    Jean-Noël Vallée

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  1. Alexandre Vallée
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  2. Yves Lecarpentier
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  3. Rémy Guillevin
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  4. Jean-Noël Vallée
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Correspondence to Alexandre Vallée.

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Vallée, A., Lecarpentier, Y., Guillevin, R. et al. Opposite Interplay Between the Canonical WNT/β-Catenin Pathway and PPAR Gamma: A Potential Therapeutic Target in Gliomas. Neurosci. Bull. 34, 573–588 (2018). https://doi.org/10.1007/s12264-018-0219-5

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  • DOI: https://doi.org/10.1007/s12264-018-0219-5

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