Autotaxin in Breast Cancer: Role, Epigenetic Regulation and Clinical Implications

SIMPLE SUMMARY: Autotaxin (ATX) has been linked with the pathogenesis of several cancers and especially with breast cancer (BC). BC is one of the most common cancers among women and although significant steps have been made regarding its early detection and treatment options, challenges still remain. This review aims to summarize the current knowledge of the role and regulation of ATX in BC and to shed light on its potential for clinical applications. ABSTRACT: Autotaxin (ATX), the protein product of Ectonucleotide Pyrophosphatase Phosphodiesterase 2 (ENPP2), is a secreted lysophospholipase D (lysoPLD) responsible for the extracellular production of lysophosphatidic acid (LPA). ATX-LPA pathway signaling participates in several normal biological functions, but it has also been connected to cancer progression, metastasis and inflammatory processes. Significant research has established a role in breast cancer and it has been suggested as a therapeutic target and/or a clinically relevant biomarker. Recently, ENPP2 methylation was described, revealing a potential for clinical exploitation in liquid biopsy. The current review aims to gather the latest findings about aberrant signaling through ATX-LPA in breast cancer and discusses the role of ENPP2 expression and epigenetic modification, giving insights with translational value.