Lecarpentier Yves, Claes Victor, Vallée Alexandre, Hébert Jean-Louis
Centre de Recherche Clinique, Hôpital de Meaux, Meaux, France.
Department of Pharmaceutical Sciences, University of Antwerp, Wilrijk, Belgium.
PPAR Res. 2017;2017:5879090. doi: 10.1155/2017/5879090. Epub 2017 Feb 19.
In both colon cancer and type 2 diabetes, metabolic changes induced by upregulation of the Wnt/beta-catenin signaling and downregulation of peroxisome proliferator-activated receptor gamma (PPAR gamma) may help account for the frequent association of these two diseases. In both diseases, PPAR gamma is downregulated while the canonical Wnt/beta-catenin pathway is upregulated. In colon cancer, upregulation of the canonical Wnt system induces activation of pyruvate dehydrogenase kinase and deactivation of the pyruvate dehydrogenase complex. As a result, a large part of cytosolic pyruvate is converted into lactate through activation of lactate dehydrogenase. Lactate is extruded out of the cell by means of activation of monocarboxylate lactate transporter-1. This phenomenon is called Warburg effect. PPAR gamma agonists induce beta-catenin inhibition, while inhibition of the canonical Wnt/beta-catenin pathway activates PPAR gamma.
在结肠癌和2型糖尿病中，Wnt/β-连环蛋白信号上调和过氧化物酶体增殖物激活受体γ（PPARγ）下调所引发的代谢变化，可能有助于解释这两种疾病为何常常同时出现。在这两种疾病中，PPARγ均下调，而经典的Wnt/β-连环蛋白途径则上调。在结肠癌中，经典Wnt系统的上调会诱导丙酮酸脱氢酶激酶激活，丙酮酸脱氢酶复合体失活。结果，大部分胞质丙酮酸通过乳酸脱氢酶激活而转化为乳酸。乳酸通过单羧酸乳酸转运蛋白-1激活而被挤出细胞。这种现象被称为瓦伯格效应。PPARγ激动剂可诱导β-连环蛋白抑制，而抑制经典的Wnt/β-连环蛋白途径则会激活PPARγ。
