Phospholipases in Gliomas: Current Knowledge and Future Perspectives from Bench to Bedside

Abstract

Phospholipases are essential intermediaries that work as hydrolyzing enzymes of phospholipids (PLs), which represent the most abundant species contributing to the biological membranes of nervous cells of the healthy human brain. They generate different lipid mediators, such as diacylglycerol, phosphatidic acid, lysophosphatidic acid, and arachidonic acid, representing key elements of intra- and inter-cellular signaling and being involved in the regulation of several cellular mechanisms that can promote tumor progression and aggressiveness. In this review, it is summarized the current knowledge about the role of phospholipases in brain tumor progression, focusing on low- and high-grade gliomas, representing promising prognostic or therapeutic targets in cancer therapies due to their influential roles in cell proliferation, migration, growth, and survival. A deeper understanding of the phospholipases-related signaling pathways could be necessary to pave the way for new targeted therapeutic strategies.

Keywords: brain tumors; gliomas; phospholipases; prognostic biomarker; therapeutic target.

Figure 1

Graphic representation of phospholipases’ cleavage sites on phospholipids, the most abundant species contributing to the biological membranes of nervous cells, and their respective products. Each phospholipase with a relative cleavage site (shown with scissors) and reaction products is represented by a specific color (from the left to the right of the figure: PLD in purple, PLC in green, PLA₂ in orange, and PLA₁ in blue). X: functional group. O: oxygen; P: phosphorus; C: carbon; H: hydrogen; R: fatty acid tails. Phospholipase B is not shown in the figure, as it is not the subject of study in this paper.