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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。
With the further research on Wnt / β-catenin and NF-κB signaling pathway in recent years, it is found that phospholipase D (PLD) as a downstream target gene is closely related to tumor formation and metastasis. Recent studies show that Wnt / β-catenin and NF-κB signaling pathway mediates PLD expression, while also enhancing PLD activity. PLD / phosphatidic acid, as an important regulatory factor, enhances the transcriptional activity of β-catenin / T cytokines and NF-κB by targeting and feedback regulation of the cycle, and promotes downstream target genes including cyclin D1, cmyc, Survivin, vascular endothelial growth factor and cyclooxygenase 2, while inhibitors of PLD / phosphatidic acid can reverse the above effects and exhibit significant antitumor effects. Therefore, PLD / phosphatidic acid signaling pathway is expected to become a new target for cancer treatment.