The Role of Enolase in Tissue Invasion and Metastasis of Pathogens and Tumor Cells

Recent studies have revealed that a glycolytic enzyme, enolase (ENO), is involved in many different physiological and pathophysiological conditions. ENO can be detected in many prokaryotic and eukaryotic cells, and is localized in cytoplasm, cell surface and nucleus of various mammalian cells to possibly mediate distinct functions. The surface ENO acts as a plasminogen-binding receptor. Upon cleavage by plasminogen activator, plasminogen is converted to plasmin that can activate collagenase and degrade fibrin and several extracellular matrix proteins. These events are critical in the resolving of fibrous tissue and the invasion of cells through stroma. By concentrating plasminogen on the surface with ENO, cells are provided with a readily source of proteolytic enzymes to assist their penetration of extracellular matrix. Many pathogens, immune cells and tumor cells appear to adopt this strategy for tissue invasion, which may be essential in systemic infection of pathogens, tissue patrolling of immune cells, and metastasis of tumor cells. Surface ENO on Gram-positive bacteria is considered to be a virulence factor. A higher expression of one isoform of mammalian ENO, ENO1 (alpha-enolase), in tumors is associated with shorter progression-free and overall survival of cancer patients with non-small cell lung carcinoma. Since ENO is present on the surface of many invasive pathogens and tumor cells and plays an important role in tissue invasion and metastasis, ENO may serve as a diagnostic/prognostic factor or a target of therapy of certain infections and cancers.