Progress in reguIation of phosphoIipase D mediated by Wnt/β-catenin and NF-κB signaIing pathways and its reIationships with tumorigenesis / 中国药理学与毒理学杂志

ABSTRACT

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.