Regulatory Roles of Six-Transmembrane Epithelial Antigen of the Prostate Family Members in the Occurrence and Development of Malignant Tumors

Abstract

The human six-transmembrane epithelial antigen of the prostate (STEAP) proteins, which include STEAP1–4 and atypical STEAP1B, contain six transmembrane domains and are located in the cell membrane. STEAPs are considered archaeal metal oxidoreductases, based on their heme groups and F420H2:NADP+ oxidoreductase (FNO)-like structures, and play an important role in cell metal metabolism. Interestingly, STEAPs not only participate in biological processes, such as molecular transport, cell cycling, immune response, and intracellular and extracellular activities, but also are closely related to the occurrence and development of several diseases, especially malignant tumors. Up to now, the expression patterns of STEAPs have been found to be diverse in different types of tumors, with controversial participation in different aspects of malignancy, such as cell proliferation, migration, invasion, apoptosis, and therapeutic resistance. It is clinically important to explore the potential roles of STEAPs as new immunotherapeutic targets for the treatment of different malignant tumors. Therefore, this review focuses on the molecular mechanism and function of STEAPs in the occurrence and development of different cancers in order to understand the role of STEAPs in cancer and provide a new theoretical basis for the treatment of diverse cancers.

Bispecific Antibody-Based Immune-Cell Engagers and Their Emerging Therapeutic Targets in Cancer Immunotherapy

“…It is highly overexpressed in various cancers, and particularly in prostate cancer, wherein it is involved in the regulation of various functions, such as cancer-cell invasion and proliferation, as well as tumorigenesis [ 98 , 99 ]. The knockdown of STEAP1 has been shown to inhibit T-cell growth in androgen-dependent prostate cancer [ 100 ]. Moreover, high STEAP1 expression is closely associated with poor outcomes in patients with prostate cancer [ 101 ].…”

Antibody-drug conjugates: beyond current approvals and potential future strategies

“…Other emerging antigen targets of interest in prostate cancer specific ADC development are STEAP1 and Trop-2. STEAP1 belongs to a family of transmembrane proteins and is upregulated selectively in prostate cancer, with its abnormal expression reportedly related to several oncogenic pathways [ 78 ]. DSTP3086S is a humanized IgG1 anti-STEAP1 monoclonal antibody conjugated to MMAE and was assessed in a phase I dose escalation study [ 79 ].…”

EFEMP1 binds to STEAP1 to promote osteosarcoma proliferation and invasion via the Wnt/β-catenin and TGF-β/Smad2/3 signal pathways

“…They participate in molecular transport, cell growth, immune responses, and other biological processes. They regulate the growth of tumor cells via intercellular communication and participate in invasion and metastasis in a variety of tumors [5] . Studies have shown that in addition to prostate cancer, STEAP1 is also highly expressed in glioma [6] , ovarian cancer [7] , gastric cancer [8] , and Ewing's sarcoma [9] .…”