Roles of the hepcidin–ferroportin axis and iron in cancer

Hepcidin is a low-molecular-weight hepatic peptide that regulates iron homeostasis, and acts by causing the degradation of its receptor, the cellular iron exporter ferroportin. On the basis of the major role of the hepcidin-ferroportin axis in iron regulation, recently several studies have discussed its expression and influence on the development and prognosis of cancer. Iron plays a pivotal role in homeostasis. However, insights into the mechanisms of normal iron regulation have provided a new perspective on the basic mechanisms, biological rationale, and pathophysiologic implications of changes in iron metabolism in cancer. Besides being a crucial stimulus for cancer, iron dysfunction also causes cancer-related anemia. In this review, we discuss aspects of the hepcidin-ferroportin axis and iron regulation, as well as the inherent connections between them in cancer. We also attempt to consider the possibility in theory of novel targets for further individualized therapy. However, many molecular mechanisms and functions of these regulators remain unclear.