Lipid signaling network was proposed as a potential target for
cancer prevention and treatment. Several recent studies revealed that
phospholipid metabolising
enzyme,
phospholipase A2 (PLA2), is a critical regulator of
cancer accelerating pathologies and apoptosis in several types of
cancers. In addition to functioning as an
enzyme, PLA2 can activate a
phospholipase A2 receptor (PLA2R1) in plasma membrane. While the list of PLA2 targets extends to
glucose homeostasis, intracellular energy balance, adipocyte development, and hepatic lipogenesis, the PLA2R1 downstream effectors are few and scarcely investigated. Among the most addressed PLA2R1 effects are regulation of pro-inflammatory signaling, autoimmunity, apoptosis, and senescence. Localized in glomeruli podocytes, the receptor can be identified by circulating anti-PLA2R1
autoantibodies leading to development of
membranous nephropathy, a strong autoimmune inflammatory cascade. PLA2R1 was shown to induce activation of
Janus-kinase 2 (JAK2) and
estrogen-related receptor α (ERRα)-controlled
mitochondrial proteins, as well as increasing the accumulation of
reactive oxygen species, thus leading to apoptosis and senescence. These findings indicate the potential role of PLA2R1 as
tumor suppressor. Epigenetic investigations addressed the role of DNA methylation, histone modifications, and specific
microRNAs in the regulation of PLA2R1 expression. However, involvement of PLA2R1 in suppression of malignant growth and
metastasis remains controversial. In this review, we summarize the recent findings that highlight the role of PLA2R1 in the regulation of
carcinogenesis-related intracellular signaling.