Stimuli and signaling pathways involved in the translocation of ?-enolase to plasma membrane in non tumorigenic and cancer breast cells

Alpha-enolase is a highly conserved glycolytic enzyme involved in multiple functions. Besides the mainly cytoplasmic localization, the protein has been detected on the cell surface of prokaryotic and eukaryotic cells, where it functions as a plasminogen receptor. Plasminogen bound to the cell membrane activates the enzyme system involved in systemic infection and cell spreading by degrading fibrin and extracellular matrix. Elevated expression of ?-enolase has been observed in many tumor types and its surface expression has been reported in lung, pancreatic and breast cancer. Recently, involvement of surface ?-enolase in invasion and metastasis has been demonstrated in lung cancer, although the molecular mechanisms of its translocation to the cell surface remain elusive. In order to investigate how ?-enolase moves to the plasma membrane and to identify the signaling pathways involved in this process, we stimulated mammary epithelial and breast cancer cells with receptor ligands and analyzed variations in the level of surface ?-enolase. In this study, we show that Epidermal Growth Factor (EGF) and pro-inflammatory endotoxin Lipopolysaccharide (LPS) treatments up-regulate the cell surface expression of ?-enolase. In addition, both in non tumorigenic and cancer breast cells we observed that EGF- and LPS-induced cell motility is correlated with an increased level of ?-enolase on the plasma membrane, consistent with the enolase function of plasminogen receptor. LPS-induced cell surface expression of ?-enolase has been well documented in monocytes during the inflammatory response, here, we unravel for the first time the putative signaling pathways underlying ?-enolase translocation to the cell membrane in mammary epithelial cells.