cPLA2 α mediates TGF- β-induced epithelial–mesenchymal transition in breast cancer through PI3k/Akt signaling

Abstract

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 A2 α (cPLA2 α) has been shown to participate in a series of biological processes including inflammation and cancer development. However, the role and molecular mechanism of cPLA2 α in breast cancer EMT and metastasis remain enigmatic. In this study, we found that cPLA2 α was commonly overexpressed in most human breast cancer tissues and significantly correlated with a poor prognosis for human breast cancer. Functional studies demonstrated that cPLA2 α overexpression was significantly associated with elevated migration and invasion in MDA-MB-231 and T47D cells. Conversely, reduced cPLA2 α expression strongly attenuated metastasis and the EMT program of MDA-MB-231 cells. Further study found that knockdown of cPLA2 α in MDA-MB-231 cells inhibited TGF- β-induced EMT through the PI3K/Akt signaling pathway. Animal experiments revealed that cPLA2 α downregulation in MDA-MB-231 cells markedly restrained tumorigenesis and metastasis in vivo. This study indicates the potential role of cPLA2 α in breast cancer metastasis and indicates that this molecule is a promising therapeutic target for breast cancer.