PLA2G7/PAF-AH as Potential Negative Regulator of the Wnt Signaling Pathway Mediates Protective Effects in BRCA1 Mutant Breast Cancer

Abstract

Past studies have confirmed that aberrant activation of the Wnt/β-catenin signaling is associated with tumorigenesis and metastasis in breast cancer, while the role of platelet-activating factor acetylhydrolase (PLA2G7/PAF-AH) in this signaling pathway remains unclear. In this study, we analyze the functional impact of PAF-AH on BRCA1 mutant breast cancer and explore its relationship to the Wnt signaling pathway. By performing immunohistochemistry, PAF-AH expression and β-catenin expression were examined in both BRCA1 WT and BRCA1 mutant breast cancer specimens. The BRCA1 mutant breast cancer cell line HCC1937 was used for in vitro experiments to assess the impact of PAF-AH on cellular functions. The intracellular distribution of β-catenin depending on PLA2G7/PAF-AH expression was investigated by immunocytochemistry. Significantly higher nuclear expression levels of PAF-AH were found in BRCA1 mutant tissue specimens than in BRCA1 WT samples. Cell viability, proliferation, and the motility rate of HCC1937 were significantly enhanced after PLA2G7 silencing, which indicated a protective role of PAF-AH in breast cancer. Nuclear PAF-AH expressed correlatedly with membranous β-catenin. PLA2G7 silencing provoked the β-catenin translocation from the membrane to the nucleus and activated Wnt signaling downstream genes. Our data showed a protective effect of high PAF-AH expression in BRCA1 mutant breast cancer. PAF-AH may achieve its protective effect by negatively regulating the Wnt pathway. In conclusion, our research sheds new light on the regulatory pathways in BRCA1 mutant breast cancer.

Combination of theoretical analysis and experiments: Exploring the role of PLA2G7 in human cancers, including renal cancer

“…The significance of PLA2G7 in specific cancer types has only been partially studied to date. For example, recent literature revealed that the downregulation of PLA2G7 in a breast cancer cell line (HCC1937) promoted proliferation and migration, suggesting a vital role for PLA2G7 in cancer [ 41 ]. Additionally, PLA2G7 has been implicated in the inflammatory process and associated with tumor immunity.…”

Investigating the potential mechanism of quercetin against cervical cancer

“…Depletion of PLA2G7 reduced intestinal polyposis and tumorigenesis in APC (Min/+) mice [ 66 ]. PLAG7 exhibited protective function in breast cancer via negative regulation of the Wnt signaling pathway [ 67 ]. On the other hand, Liao et al discovered that high PLA2G7 protein level was associated with significantly longer OS than low protein level of PLA2G7 in ovarian cancer patients.…”