Yang_2025_Int.J.Oncol_67_

Lipoproteinassociated phospholipase A2 (LpPLA2), an important member of the phospholipase A2 superfamily, was originally investigated for its proinflammatory role in cardiovascular diseases. Recent studies have revealed its significant role in tumorigenesis: It can act as either a tumor promoter or a tumor suppressor depending on the context. The present review systematically outlined the dual mechanisms by which LpPLA2 contributes to cancer pathogenesis. As a tumor promoter, it promotes cancer progression via the induction of epithelialmesenchymal transition, glutathione peroxidase 4mediated resistance to ferroptosis, and vascular endothelial growth factor-dependent angiogenesis; conversely, as a tumor suppressor, it inhibits tumor growth by suppressing the Wnt/betacatenin pathway in breast cancer gene 1mutated cancers or by promoting apoptosis. Mechanistic investigations clarify the interactions between LpPLA2 and critical oncogenic pathways, such as the Notch and HIF1alpha pathways, while emphasizing the functional dichotomy that is influenced by the microenvironment. Current evidence supports the development of microenvironmentguided targeting strategies and the potential value of LpPLA2 as a prognostic biomarker and therapeutic target. These findings contribute to a theoretical framework for comprehending the contextdependent roles of LpPLA2 and may guide the development of innovative therapeutic approaches.