Xu Michael, Evans Latese, Bizzaro Candice L, Quaglia Fabio, Verrillo Cecilia E, Li Li, Stieglmaier Julia, Schiewer Matthew J, Languino Lucia R, Kelly William K
Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Department of Pharmacology, Physiology and Cancer Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Cancers (Basel). 2022 Aug 20;14(16):4034. doi: 10.3390/cancers14164034.
Six-Transmembrane Epithelial Antigen of the Prostate 1-4 (STEAP1-4) compose a family of metalloproteinases involved in iron and copper homeostasis and other cellular processes. Thus far, five homologs are known: STEAP1, STEAP1B, STEAP2, STEAP3, and STEAP4. In prostate cancer, STEAP1, STEAP2, and STEAP4 are overexpressed, while STEAP3 expression is downregulated. Although the metalloreductase activities of STEAP1-4 are well documented, their other biological functions are not. Furthermore, the properties and expression levels of STEAP heterotrimers, homotrimers, heterodimers, and homodimers are not well understood. Nevertheless, studies over the last few decades have provided sufficient impetus to investigate STEAP1-4 as potential biomarkers and therapeutic targets for prostate cancer. In particular, STEAP1 is the target of many emerging immunotherapies. Herein, we give an overview of the structure, physiology, and pathophysiology of STEAP1-4 to provide context for past and current efforts to translate STEAP1-4 into the clinic.
前列腺六跨膜上皮抗原1-4（STEAP1-4）构成了一个金属蛋白酶家族，参与铁和铜的稳态以及其他细胞过程。到目前为止，已知有五个同源物：STEAP1、STEAP1B、STEAP2、STEAP3和STEAP4。在前列腺癌中，STEAP1、STEAP2和STEAP4过表达，而STEAP3表达下调。虽然STEAP1-4的金属还原酶活性已有充分记录，但其其他生物学功能却未明确。此外，STEAP异源三聚体、同源三聚体、异源二聚体和同源二聚体的特性和表达水平也尚未完全了解。尽管如此，过去几十年的研究为将STEAP1-4作为前列腺癌的潜在生物标志物和治疗靶点进行研究提供了足够的动力。特别是，STEAP1是许多新兴免疫疗法的靶点。在此，我们概述STEAP1-4的结构、生理学和病理生理学，为过去和当前将STEAP1-4转化为临床应用的努力提供背景信息。
