Wnt/β连环素和NF-κB信号通路对磷脂酶D的调控作用及其与肿瘤关系的研究进展

Progress in regulation of phospholipase D mediated by Wnt/β-catenin and NF-κB signaling pathways and its relationships with tumorigenesis

随着近几年对Wnt/β连环素和NF-κB信号通路研究的深入,发现磷脂酶D(PLD)作为其下游共有的靶基因与肿瘤的形成和转移密切相关。最新研究表明,Wnt/β连环素和NF-κB信号通路介导PLD表达的同时,也增强了PLD活性。PLD/磷脂酸作为重要的调控因子,通过靶向及正反馈循环调控机制的方式增强β连环素/T细胞因子和NF-κB的转录活性,促进下游靶基因,包括细胞周期蛋白D1、cmyc、存活蛋白、血管内皮生成因子和环氧化酶2的转录和表达,而PLD/磷脂酸的抑制剂可逆转以上作用且表现出显著的抗肿瘤效应。因此,PLD/磷脂酸信号通路有望成为癌症治疗的新靶点。

Over the last few years,elevated phospholipase D（PLD）expression and activity found to be mediated by Wnt/ β-catenin and NF-κB signaling axis sharing the same downstream genes have been involved in tumorigenesis,controlling cancer cell invasion and metastasis. New studies have revealed that Wnt signaling/ NF-κB signaling can induce PLD upregulation and increased enzymatic activ-ity. PLD/ PLD-generated phosphatidic acid（ PA）,as a critical regulator,might positively modulate β-catenin-dependent T-cell factor and NF-κB transcriptional activity via a targeted motif and a positive feed-back loop to reinforce pathway output including cyclin D1 ,c-myc,survivin,vascular endothelial growth factor and cyclooxygenase-2,while PLD/ PA inhibitors can reverse all the effect mentioned above and achieve significantly better anticancer effects. The PLD/ PA signaling pathway can be a novel therapeutic target for the treatment of cancer.