Beyond ENO1, Emerging Roles and Targeting Strategies of Other Enolases in Cancers

Aerobic glycolysis is a hallmark property of cancer metabolism. Enolase is a glycolytic enzyme that catalyzes the conversion of 2-phosphoglycerate into phosphoenolpyruvate. In mammals, enolases exist in three isoforms, encoded by the genes ENO1, ENO2, and ENO3. The altered expression of enolases is a common occurrence in various types of cancer. Although most published studies on enolases have predominantly focused on the role of ENO1 in cancer, ENO2 and ENO3 have recently emerged as crucial regulatory molecules in cancer development. Significant progress has been made in understanding their multifaceted roles in oncogenesis. In this comprehensive review, we provide an overview of the structure, subcellular localization, diagnostic and prognostic significance, biological functions, and molecular mechanisms of ENO2 and ENO3 in cancer progression. The importance of enolase in cancer development makes it a novel therapeutic target for clinical applications. Furthermore, we discuss anticancer agents designed to target enolases and summarize their anticancer efficacy in both in vitro and in vivo studies.