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

  • Alexandre Vallée
  • Yves Lecarpentier
  • Rémy Guillevin
  • Jean-Noël Vallée
Review

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.

Keywords

WNT/beta-catenin pathway PPAR gamma Glioma STAT3 pathway PI3K/Akt pathway NSAID Curcumin 

Notes

Compliance with Ethical Standards

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest.

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Copyright information

© Shanghai Institutes for Biological Sciences, CAS and Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Alexandre Vallée
    • 1
    • 2
  • Yves Lecarpentier
    • 3
  • Rémy Guillevin
    • 4
  • Jean-Noël Vallée
    • 1
    • 5
  1. 1.Laboratory of Mathematics and Applications, Unités Mixtes de Recherche (UMR), Centre National de la Recherche Scientifique (CNRS) 7348University of PoitiersPoitiersFrance
  2. 2.Délégation à la Recherche Clinique et à l’Innovation (DRCI)Hôpital FochSuresnesFrance
  3. 3.Centre de Recherche CliniqueGrand Hôpital de l’Est FrancilienMeauxFrance
  4. 4.DACTIM, UMR CNRS 7348University of Poitiers et CHU de PoitiersPoitiersFrance
  5. 5.CHU Amiens PicardieUniversity of Picardie Jules VerneAmiensFrance

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