The STEAP protein family: Versatile oxidoreductases and targets for cancer immunotherapy with overlapping and distinct cellular functions

The human six-transmembrane epithelial antigen of the prostate (STEAP) protein family contains at least five homologous members. The necessity of multiple homologous STEAP proteins is still unclear, but their peculiar and tissue-specific expression suggests that they are assigned to distinct functional tasks. This concept is supported by the fact that especially STEAP1, and to a lesser extent STEAP2 and -4, are highly over-expressed in many different cancer entities, while being only minimally expressed in a few normal tissues. Despite their very similar domain organisation, STEAP3 seems to act as a potent metalloreductase essential for physiological iron uptake and turnover, while in particular STEAP4 appears to be rather involved in responses to nutrients and inflammatory stress, fatty acid and glucose metabolism. Moreover, individual STEAP proteins possess overlapping functions important for growth and survival of cancer cells. Due to their membrane-bound localisation and their high expression in many different cancers such as prostate, breast and bladder carcinoma as well as Ewing's sarcoma, STEAP proteins have been recognised and utilised as promising targets for cell- and antibody-based immunotherapy. This review summarises our present knowledge of the individual members of the human STEAP family and highlights the functional differences between them.