STEAP1 Membrane Protein Introduction

Introduction of STEAP1

Six-transmembrane epithelial antigen of prostate 1 (STEAP1), is a cell surface antigen overexpressed in multiple cancers and is associated with malignancy and disease prognosis. The protein is encoded by the STEAP1 gene and has six transmembrane (TM) helices. STEAP1 is strongly expressed in many human cancers, including prostate cancer, colon cancer, bladder cancer and liver cancer, and Ewing's sarcoma. STEAP1 expression levels are higher in the early stages of prostate cancer than the late stage, and the intensity of STEAP1 staining correlates with tumor grade and appears to increase with malignancy. Since normal tissues have little or no expression of STEAP1, these studies suggest that STEAP1 may play an important role in cancer progression, but little is known about the function of STEAP1.

The Function of STEAP1 Membrane Protein

The six transmembrane epithelial antigen (STEAP1) of the prostate is significantly up-regulated in prostate cancer and has a small degree of up-regulation in other types of cancer. STEAP1 is rarely expressed in normal tissues and is completely confined to the prostate, making it a very promising biomarker and immunotherapeutic target for cancers. It is mainly located on the plasma membrane of epithelial cells, but it has also been found to be dispersed in the cytoplasm. STEAP1 acts as an ion channel or transporter at the cell-cell junction in the prostate and is involved in intercellular communication. Knockdown of the STEAP1 gene can promote apoptosis mediated by an extrinsic pathway or an endogenous pathway. Because of its specific membrane-bound localization and its high expression levels in cancers, STEAP1 is considered to be a tumor-associated antigen and it may represent a potential target for therapeutic strategies.

Fig.1 Membrane topology of mammalian (rabbit) STEAP1. (Kim, 2016)

Application of STEAP1 Membrane Protein Literature

1. Gomes I.M., et al. Knockdown of STEAP1 inhibits cell growth and induces apoptosis in LNCaP prostate cancer cells counteracting the effect of androgens. Medical Oncology. 2018, 35(3):40. PubMed ID:29464393
   
   

   This article finds that the molecular effects of knockout of the STEAP1 gene may be unrelated to DHT treatment, and blocking STEAP1 may be a strategy to activate cancer cell apoptosis and prevent proliferation and anti-apoptosis.

2. Barrocaferreira J., et al. Targeting STEAP1 protein in human cancer: current trends and future challenges. Current Cancer Drug Targets. 2018, 18(3):222-230. PubMed ID:28460619
   
   

   This review describes the expression of STEAP1 protein in human tissues and its biochemical properties and targeting strategies, and evaluates the potential of STEAP1 as cancer therapeutic.

3. Kim K., et al. Six Transmembrane Epithelial Antigen of Prostate 1 (STEAP1) Has a Single b Heme and Is Capable of Reducing Metal Ion Complexes and Oxygen. Biochemistry. 2016, 55(48):6673-6684. PubMed ID:27792302
   
   

   This study firstly purifies mammalian (rabbit) STEAP1 in milligrams and highlights its role as a novel metal reductase and superoxide synthase, laying a solid foundation for further study of how STEAP1 activity affects cancer progression.

4. Ching-Hsiao L., et al. The Prognostic Role of STEAP1 Expression Determined via Immunohistochemistry Staining in Predicting Prognosis of Primary Colorectal Cancer: A Survival Analysis. International Journal of Molecular Sciences. 2016, 17(4). PubMed ID:27104516
   
   

   This article investigates the possible association between the expression of STEAP1 and the prognosis of colorectal cancer and suggests that the expression of STEAP1 can be used as a prognostic marker for colorectal patients.

5. Gomes I.M., et al. Expression of STEAP1 and STEAP1B in prostate cell lines, and the putative regulation of STEAP1 by post-transcriptional and post-translational mechanisms. Genes & Cancer. 2014, 5(3-4):142-51. PubMed ID:25053991
   
   

   This article shows that STEAP1 may be regulated by post-transcriptional and post-translational modifications (PTM), and PTM may be involved in the regulation of STEAP1 expression in prostate cells.

STEAP1 Preparation Options

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Reference

1. Kim K, et al. (2016). Six Transmembrane Epithelial Antigen of Prostate 1 (STEAP1) Has a Single b Heme and Is Capable of Reducing Metal Ion Complexes and Oxygen. Biochemistry. 55(48):6673-6684.

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