Phospholipases as pivotal players in signal transduction during tumorigenic processes

Phospholipases are phospholipid-hydrolyzing enzymes that generate a variety of bioactive lipid products, including arachidonic acid, diacylglycerol, and lysophospholipids, that transduce numerous cellular signaling networks associated with survival and proliferation. There exists a wide range of phospholipases, among which phospholipases A2, C, and D are known to take part in the modulation of several cancer regulatory genes. A constellation of extracellular and intracellular signals activates these phospholipases, which, in turn, modulate the transcription of various genes and influence epigenetic regulation having a direct or indirect association with carcinogenesis. Phospholipases, however, have a dual role. On one hand, their aberrant expressions are involved in the promotion of carcinogenesis via inflammatory and growth signaling networks, while on the other hand, their genetic modulation may be involved in cancer prevention and therapy. This chapter explores phospholipase-driven various signal transduction pathways involved in carcinogenesis, their genetic and epigenetic regulation, and their management for antitumorigenic efficacy.