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.