Thermodynamics in cancers: opposing interactions between PPAR gamma and the canonical WNT/beta-catenin pathway.
Thermodynamics in cancers: opposing interactions between PPAR gamma and the canonical WNT/beta-catenin pathway.
复制标题
癌症中的热力学：PPAR γ和经典WNT/β-连环蛋白通路之间的相互作用。
DOI：
10.1186/s40169-017-0144-7
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发表时间：
2017-12
影响因子：
10.6
通讯作者：
Hébert JL
中科院分区：
文献类型：
--
作者：
Lecarpentier Y;Claes V;Vallée A;Hébert JL
癌细胞是许多代谢和热力学异常的部位。我们专注于此审查之间的相互作用的经典WNT/β-连环蛋白通路和过氧化物酶体增殖物激活受体γ（PPAR γ）在癌症和它们的影响，从能量和代谢的角度来看。在许多组织中，PPAR γ激活诱导β-连环蛋白途径的抑制，而经典WNT/β-连环蛋白途径的激活使PPAR γ失活。在大多数但不是所有的癌症中，PPAR γ下调，而WNT/β-连环蛋白通路上调。在癌细胞中，WNT/β-连环蛋白信号传导的上调诱导关键代谢酶的显著变化，从而改变其热力学行为。这导致丙酮酸脱氢酶激酶1（PDK-1）和单羧酸乳酸转运蛋白的激活。因此，PDK-1的磷酸化抑制丙酮酸脱氢酶复合物（PDH）。因此，大部分丙酮酸不能在线粒体中转化为乙酰辅酶A（乙酰辅酶A），只有一部分乙酰辅酶A可以进入三羧酸循环。这导致有氧糖酵解，尽管氧气的可用性。这种现象被称为瓦尔堡效应。胞质丙酮酸转化为乳酸。WNT/β-连环蛋白途径诱导参与细胞增殖的基因的转录，即，MYC和细胞周期蛋白D1。这最终促进细胞生长和增殖所必需的核苷酸、蛋白质和脂质的合成。在癌症中，PI 3 K-AKT途径的激活诱导有氧糖酵解的增加。此外，前列腺素E2通过激活经典WNT途径也在癌症中发挥作用。此外，在许多癌细胞中，PPAR γ下调。此外，PPAR γ有助于调节一些关键的昼夜节律基因。在癌症中，观察到昼夜节律（CR）调节的异常。CR是耗散结构，在远离平衡态热力学中起着关键作用。在癌症中，代谢、热力学和CR密切相关。
Cancer cells are the site of numerous metabolic and thermodynamic abnormalities. We focus this review on the interactions between the canonical WNT/beta-catenin pathway and peroxisome proliferator-activated receptor gamma (PPAR gamma) in cancers and their implications from an energetic and metabolic point of view. In numerous tissues, PPAR gamma activation induces inhibition of beta-catenin pathway, while the activation of the canonical WNT/beta-catenin pathway inactivates PPAR gamma. In most cancers but not all, PPAR gamma is downregulated while the WNT/beta-catenin pathway is upregulated. In cancer cells, upregulation of the WNT/beta-catenin signaling induces dramatic changes in key metabolic enzymes that modify their thermodynamic behavior. This leads to activation of pyruvate dehydrogenase kinase1 (PDK-1) and monocarboxylate lactate transporter. Consequently, phosphorylation of PDK-1 inhibits the pyruvate dehydrogenase complex (PDH). Thus, a large part of pyruvate cannot be converted into acetyl-coenzyme A (acetyl-CoA) in mitochondria and only a part of acetyl-CoA can enter the tricarboxylic acid cycle. This leads to aerobic glycolysis in spite of the availability of oxygen. This phenomenon is referred to as the Warburg effect. Cytoplasmic pyruvate is converted into lactate. The WNT/beta-catenin pathway induces the transcription of genes involved in cell proliferation, i.e., MYC and CYCLIN D1. This ultimately promotes the nucleotide, protein and lipid synthesis necessary for cell growth and multiplication. In cancer, activation of the PI3K-AKT pathway induces an increase of the aerobic glycolysis. Moreover, prostaglandin E2 by activating the canonical WNT pathway plays also a role in cancer. In addition in many cancer cells, PPAR gamma is downregulated. Moreover, PPAR gamma contributes to regulate some key circadian genes. In cancers, abnormalities in the regulation of circadian rhythms (CRs) are observed. CRs are dissipative structures which play a key-role in far-from-equilibrium thermodynamics. In cancers, metabolism, thermodynamics and CRs are intimately interrelated.