Opposite Interplay Between the Canonical WNT/β-Catenin Pathway and PPAR Gamma: A Potential Therapeutic Target in Gliomas.
10.1007/s12264-018-0219-5
- Author:
Alexandre VALLÉE
1
;
Yves LECARPENTIER
2
;
Rémy GUILLEVIN
3
;
Jean-Noël VALLÉE
4
Author Information
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.g.vallee@gmail.com.
2. Centre de Recherche Clinique, Grand Hôpital de l'Est Francilien, Meaux, France.
3. DACTIM, UMR CNRS 7348, University of Poitiers et CHU de Poitiers, Poitiers, France.
4. Laboratory of Mathematics and Applications, Unités Mixtes de Recherche (UMR), Centre National de la Recherche Scientifique (CNRS) 7348, University of Poitiers, Poitiers, France.
- Publication Type:Journal Article
- Keywords:
Curcumin;
Glioma;
NSAID;
PI3K/Akt pathway;
PPAR gamma;
STAT3 pathway;
WNT/beta-catenin pathway
- MeSH:
Animals;
Brain Neoplasms;
metabolism;
therapy;
Dacarbazine;
analogs & derivatives;
pharmacology;
Down-Regulation;
drug effects;
Glioma;
metabolism;
therapy;
Humans;
PPAR gamma;
metabolism;
Temozolomide;
Wnt Signaling Pathway;
drug effects;
physiology
- From:Neuroscience Bulletin
2018;34(3):573-588
- CountryChina
- Language:English
-
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.
