cPLA2α mediates TGF-β-induced epithelial-mesenchymal transition in breast cancer through PI3k/Akt signaling.

A high incidence of tumor recurrence and metastasis has been reported in breast cancer patients; nevertheless, the underlying molecular mechanisms are largely unknown. Epithelial-mesenchymal transition (EMT), which is induced by transforming growth factor-β (TGF-β), has been implicated in tumorigenesis and breast cancer metastasis. EMT events are now directly associated with tumor metastasis, and this progress is dependent on the inflammatory microenvironment. Cytosolic phospholipase A2α (cPLA2α) has been shown to participate in a series of biological processes including inflammation and cancer development. However, the role and molecular mechanism of cPLA2α in breast cancer EMT and metastasis remain enigmatic. In this study, we found that cPLA2α was commonly overexpressed in most human breast cancer tissues and significantly correlated with a poor prognosis for human breast cancer. Functional studies demonstrated that cPLA2α overexpression was significantly associated with elevated migration and invasion in MDA-MB-231 and T47D cells. Conversely, reduced cPLA2α expression strongly attenuated metastasis and the EMT program of MDA-MB-231 cells. Further study found that knockdown of cPLA2α in MDA-MB-231 cells inhibited TGF-β-induced EMT through the PI3K/Akt signaling pathway. Animal experiments revealed that cPLA2α downregulation in MDA-MB-231 cells markedly restrained tumorigenesis and metastasis in vivo. This study indicates the potential role of cPLA2α in breast cancer metastasis and indicates that this molecule is a promising therapeutic target for breast cancer.