Fig. 9

Proposed mechanism of PNPLA8 in the regulation of phospholipid metabolism resulting in increased migration and proliferation in TNBC through the activation of PI3K/Akt/GSK3β and MAPK pathways. Our data suggest that the upregulation of PNPLA8 and downregulation of LPCAT4 promotes the hydrolysis of phospholipids. Acting as both phospholipase and lysophospholipase, PNPLA8 mediates the production of lysophospholipids and GPC, releasing arachidonic acid, leading to elevated PGE2 and 20-HETE from arachidonic acid through the cyclooxygenase and cytochrome P450 pathways, respectively. Secreted PGE2 and 20-HETE can bind to prostaglandin E2 receptors (EP) and G protein-coupled receptors (GPCR), respectively, then activate the PI3K/Akt and MAPK/Erk signaling pathways, promoting cell proliferation and migration in triple-negative breast cancer