Functional role of phospholipase D in apoptosis and cancer

Phospholipase D (PLD) is a type of transphosphatidylase that hydrolyzes phosphatidylcholine (PC) to produce soluble choline and phosphatidic acid (PA), a signaling molecule. PLD is essential for signal transduction, cell proliferation, and antiapoptotic activities. Blocking PLD during therapy can make cancer cells more susceptible to chemotherapy. PLD levels are increased in a number of human cancers, making it an important marker for inflammation and cancer. It has been proposed that, by inhibiting p53-mediated apoptosis, PLD aids in the development of cancer. Neurotransmitters, hormones, small monomeric GTPases, and lipids are major contributors to and regulators of PLD's function. Other than its role in apoptosis and cancer, PLD has been linked to a wide variety of physiological and pathological processes, including infection, tumorigenesis, chronic renal toxicity, brain and heart disorders, and neurodegenerative diseases. In this chapter, we summarize the structural, functional, and mechanistic aspects of PLD and its different isoforms. Since two of its isoforms, PLD1 and PLD2, have drawn more attention in the context of cancer and other therapeutic activities, we mainly focus on these two isoforms. We also discuss its anticancer mode of action, highlighting that it could be used as a promising target in cancer treatment and management.