Phospholipase D and Its Essential Role in Cancer

Abstract

The role of phospholipase D (PLD) in cancer development and management has been a major area of interest for researchers. The purpose of this mini-review is to explore PLD and its distinct role during chemotherapy including anti-apoptotic function. PLD is an enzyme that belongs to the phospholipase super family and is found in a broad range of organisms such as viruses, yeast, bacteria, animals, and plants. The function and activity of PLD are widely dependent on and regulated by neurotransmitters, hormones, small monomeric GTPases, and lipids. A growing body of research has shown that PLD activity is significantly increased in cancer tissues and cells, indicating that it plays a critical role in signal transduction, cell proliferation, and anti-apoptotic processes. In addition, recent studies show that PLD is a downstream transcriptional target of proteins that contribute to inflammation and carcinogenesis such as Sp1, NFκB, TCF4, ATF-2, NFATc2, and EWS-Fli. Thus, compounds that inhibit expression or activity of PLD in cells can be potentially useful in reducing inflammation and sensitizing resistant cancers during chemotherapy.

Keywords: PLD; anti-cancer drug; apoptosis; cancer; inhibitor.

Fig. 1. Structure of a PC and enzymatic reaction of PLD with PC, hydrolysis or transphosphatidylation

(A) Phosphatidylcholine, a lipid formed from a choline head, a phosphate, a glycerol and two fatty acids. (Dark gray: carbon atoms; Light gray: hydrogen atoms; Red: oxygen atoms; Violet: phosphorus atom; Blue: nitrogen atom.). (B) The model summarizes of catalytic mechanism of PLD in biochemical reaction. Catalysis proceeds via the formation of PA (a covalent enzyme) intermediate. Hydrolysis or transphosphatidylation involves nucleophillic attack on the diester phosphate group of this intermediate by water or the hydroxyl group of a primary alcohol. PA, phosphatidic acid; PC, phosphatidylcholine; PLD, phospholipase D.