Phospholipase A2 superfamily in cancer

Phospholipase A2 enzymes (PLA2s) comprise a superfamily that is generally divided into six subfamilies known as cytosolic PLA2s (cPLA2s), calcium-independent PLA2s (iPLA2s), secreted PLA2s (sPLA2s), lysosomal PLA2s, platelet-activating factor (PAF) acetylhydrolases, and adipose specific PLA2s. Each subfamily consists of several isozymes that possess PLA2 activity. The first three PLA2 subfamilies play important roles in inflammation-related diseases and cancer. In this review, the roles of well-studied enzymes sPLA2-IIA, cPLA2α and iPLA2β in carcinogenesis and cancer development were discussed. sPLA2-IIA seems to play conflicting roles and can act as a tumor suppressor or a tumor promoter according to the cancer type, but cPLA2α and iPLA2β play protumorigenic role in most cancers. The mechanisms of PLA2-mediated signal transduction and crosstalk between cancer cells and endothelial cells in the tumor microenvironment are described. Moreover, the mechanisms by which PLA2s mediate lipid reprogramming and glycerophospholipid remodeling in cancer cells are illustrated. PLA2s as the upstream regulators of the arachidonic acid cascade are generally high expressed and activated in various cancers. Therefore, they can be considered as potential pharmacological targets and biomarkers in cancer. The detailed information summarized in this review may aid in understanding the roles of PLA2s in cancer, and provide new clues for the development of novel agents and strategies for tumor prevention and treatment.