Phospholipase D meets Wnt signaling: a new target for cancer therapy.

Phospholipase D (PLD) has been increasingly recognized as a critical regulator of cell proliferation and tumorigenesis. PLD regulates downstream effectors by generating phosphatidic acid (PA), and the expression and activity of PLD are elevated in many different types of human cancer. Aberrant activation of Wnt/β-catenin signaling, followed by hyper-activation of target genes, is linked to a wide range of cancers. New studies reveal a direct connection between the PLD and the Wnt signaling pathways; PLD is a transcriptional target of β-catenin/T-cell factor (TCF) and reinforces Wnt/β-catenin signaling related with cellular transformation. In this review, we discuss the emerging importance of PLD and PA in the Wnt/β-catenin signaling network, which is associated with tumorigenesis, and suggest that the PLD/PA signaling pathway is a potential therapeutic target for the treatment of cancer.