The role of ErbB4 in cancer

The epidermal growth factor receptor family consists of four members, ErbB1 (epidermal growth factor receptor-1), ErbB2, ErbB3, and ErbB4, which all have been found to play important roles in tumor development. ErbB4 appears to be unique among these receptors, because it is the only member with growth inhibiting properties. ErbB4 plays well-defined roles in normal tissue development, in particular the heart, the nervous system, and the mammary gland system. In recent years, information on the role of ErbB4 in a number of tumors has emerged and its general direction points towards a tumor suppressor role for ErbB4. However, there are some controversies and conflicting data, warranting a review on this topic. Here, we discuss the role of ErbB4 in normal physiology and in breast, lung, colorectal, gastric, pancreatic, prostate, bladder, and brain cancers, as well as in hepatocellular carcinoma, cholangiocarcinoma, and melanoma. Understanding the role of ErbB4 in cancer is not only important for the treatment of tumors, but also for the treatment of other disorders in which ErbB4 plays a major role, e.g. cardiovascular disease.