The lipid-modifying signal transduction enzyme phospholipase D (PLD) has been proposed to have roles in oncogenic processes for well-on 30 years, with most of the early literature focused on potential functions for PLD in the biology of the tumor cells themselves. While such roles remain under investigation, evidence has also now been generated to support additional roles for PLD, in particular PLD1, in the tumor microenvironment, including effects on neoangiogenesis, the supply of nutrients, interactions of platelets with circulating cancer cells, the response of the immune system, and exosome biology. Here, we review these lines of investigation, accompanied by a discussion of the limitations of the existing studies and some cautionary notes regarding the study and interpretation of PLD function using model systems.
Keywords: Autophagy; Breast cancer; Cardiovascular; Exosomes; Immune responses; Inhibitor; Lipid signaling; Metastasis; Neoangiogenesis; PLD1; PLD2; Phospholipase D; Platelets; Tumor microenvironment; VEGF.