The Eph/Ephrin System in Hepatocellular Carcinoma: Functional Roles and Potential Therapeutic Targets

Liver cancer is ranked as the second leading cause of cancer-related death across the world, and hepatocellular carcinoma (HCC) comprises nearly 90% of all primary liver cancer cases. However, until now, the pathological mechanisms underlying HCC oncogenesis and development remains largely unclear. Eph receptors and their ephrin ligands (Eph/Ephrin system) are involved in various physiological process, such as embryogenesis, neuronal migration, immune response and vascular development. Recently, emerging evidence has showed that the Eph/Ephrin system also plays an essential role in initiation and development of multiple types of cancer, including liver cancer. The Eph/Ephrin system has been reported to contribute to cellular proliferation, apoptosis, migration, invasion, angiogenesis, stemness and drug/radiotherapy resistance in HCC. Thus, the aim of this review is to summarize the effects and underlying mechanisms of every member of this system in HCC, with special focus on assessing their therapeutic potential as drug targets.