Inhibition of cytosolic phospholipase A2 alpha increases chemosensitivity in cervical carcinoma through suppressing β-catenin signaling

Abstract

Cytosolic phospholipase A2alpha (cPLA2α) is a key mediator of tumorigenesis. In this study, by using a combination of pharmacological and genetic approaches in cell models and patient samples, we identify cPLA2α as a selective target to increase chemosensitivity in cervical cancer. We found that transcript and protein levels of cPLA2α but not other forms of cPLA2 (e.g., cPLA2β and cPLA2αδ) were consistently increased in all tested malignant cervical cancer cells and tissues compared to normal counterparts, suggesting that cPLA2α upregulation is a common feature in cervical cancer. We further found that promoting growth and survival rather than invasion were the predominant roles of cPLA2α on cervical cancer. In addition, chemotherapeutic agents achieved ~100% inhibition efficacy in cPLA2α-depleted cervical cancer cells, demonstrating the important role of cPLA2α in chemoresistance. Importantly, we identify that β-catenin is critically involved in the molecular mechanism of cPLA2α’s action in cervical cancer. In summary, our work demonstrates the multiple essential roles of cPLA2α in cervical cancer, particularly in chemoresistance, via a β-catenin-dependent manner. Our work also suggests that targeting cPLA2α has a therapeutic value in overcoming chemoresistance in cervical cancer or other cPLA2α-regulated cancers.