Phospholipase D (
PLD) is a
membrane protein with a double role: maintenance of the structural integrity of cellular or intracellular membranes and involvement in cell signaling through the product of the catalytic reaction, PA, and through
protein-
protein interaction with a variety of partners. Cross-talk during
PLD signaling occurs with other
cancer regulators (Ras, PDGF, TGF and
kinases). Elevation of either PLD1 or PLD2 (the two mammalian
isoforms of
PLD) is able to transform fibroblasts and contribute to
cancer progression. Elevated total
PLD activity, as well as overexpression, is present in a wide variety of
cancers such as gastric, colorectal, renal, stomach, esophagus, lung and breast.
PLD provides survival signals and is involved in migration, adhesion and invasion of
cancer cells, and all are increased during
PLD upregulation or, conversely, they are decreased during
PLD loss of function. Eventhough the end results of
PLD action as relates to downstream signaling mechanisms are still currently being elucidated, invasion, a pre-requisite for
metastasis, is directly affected by
PLD. This review will introduce the classical mammalian
PLD's, PLD1 and PLD2, followed by the mechanisms of intracellular regulation and a status of current investigation in the crucial involvement of
PLD in
cancer, mostly through its role in cell migration, invasion and
metastasis, that has grown exponentially in the last few years.