Thermodynamics in Gliomas: Interactions between the Canonical WNT/Beta-Catenin Pathway and PPAR Gamma.
TLDR
In gliomas, metabolism, thermodynamics, and circadian rhythms are tightly interrelated and Circadian rhythms play a key role in far-from-equilibrium thermodynamics through their interactions with WNT/beta-catenin pathway and PPAR gamma.Abstract:
Gliomas cells are the site of numerous metabolic and thermodynamics abnormalities with an increasing entropy rate which is characteristic of irreversible processes driven by changes in Gibbs energy, heat production, intracellular acidity, membrane potential gradient, and ionic conductance We focus our review on the opposing interactions observed in glioma between the canonical WNT/beta-catenin pathway and PPAR gamma and their metabolic and thermodynamic implications In gliomas, WNT/beta-catenin pathway is upregulated while PPAR gamma is downregulated Upregulation of WNT/beta-catenin signaling induces changes in key metabolic enzyme that modify their thermodynamics behavior This leads to activation pyruvate dehydrogenase kinase 1(PDK-1) and monocarboxylate lactate transporter 1 (MCT-1) Consequently, phosphorylation of PDK-1 inhibits pyruvate dehydrogenase complex (PDH) Thus, a large part of pyruvate cannot be converted into acetyl-CoA in mitochondria and in TCA (tricarboxylic acid) cycle This leads to aerobic glycolysis despite the availability of oxygen, named Warburg effect Cytoplasmic pyruvate is, in major part, converted into lactate The WNT/beta-catenin pathway induces also the transcription of genes involved in cell proliferation, cell invasiveness, nucleotide synthesis, tumor growth, and angiogenesis, such as c-Myc, cyclin D1, PDK In addition, in gliomas cells, PPAR gamma is downregulated, leading to a decrease in insulin sensitivity and an increase in neuroinflammation Moreover, PPAR gamma contributes to regulate some key circadian genes Abnormalities in the regulation of circadian rhythms and dysregulation in circadian clock genes are observed in gliomas Circadian rhythms are dissipative structures, which play a key role in far-from-equilibrium thermodynamics through their interactions with WNT/beta-catenin pathway and PPAR gamma In gliomas, metabolism, thermodynamics, and circadian rhythms are tightly interrelatedread more
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Crosstalk Between Peroxisome Proliferator-Activated Receptor Gamma and the Canonical WNT/β-Catenin Pathway in Chronic Inflammation and Oxidative Stress During Carcinogenesis.
TL;DR: In this paper, the authors explain the opposite and unidirectional profile of the canonical WNT/β-catenin signaling and peroxisome proliferator-activated receptor gamma (PPARγ) in these three frequent and morbid processes that potentiate each other.
Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogeni
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Targeting the Canonical WNT/β-Catenin Pathway in Cancer Treatment Using Non-Steroidal Anti-Inflammatory Drugs.
TL;DR: The administration of NSAIDs in cancer treatment would appear to be an interesting therapeutic strategy, which acts through their role in regulating WNT/β-catenin pathway and PPARγ activity levels.
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