Opposite Interplay Between the Canonical WNT/β-Catenin Pathway and PPAR Gamma: A Potential Therapeutic Target in Gliomas / 神经科学通报·英文版
Neuroscience Bulletin
;
(6): 573-588, 2018.
Article
in English
| WPRIM
| ID: wpr-777032
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
Physiology
/
Therapeutics
/
Brain Neoplasms
/
Down-Regulation
/
Dacarbazine
/
PPAR gamma
/
Wnt Signaling Pathway
/
Temozolomide
/
Glioma
Limits:
Animals
/
Humans
Language:
English
Journal:
Neuroscience Bulletin
Year:
2018
Type:
Article
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