STEAP2 Membrane Protein Introduction

Introduction of STEAP2

The STEAP2 protein, a member of the Six-transmembrane epithelial antigen of the prostate (STEAP) protein family, is mainly encoded by the STEAP2 gene that is located on chromosome 7q21.13 and contains 6 exons and 5 introns. STEAP2 contains six transmembrane domains located in the endoplasmic reticulum or plasma membrane. The open reading frame of the STEAP2 gene is located in the third exon and produces a protein of 490 amino acids with a predicted molecular mass of 56 kilodaltons. Human tissue expresses four different mRNA transcripts, three of which are produced by alternative splicing of the last exon. STEAP family of prostate contains four members, and STEAP2 has significant sequence homology with the other three members. In normal tissues, STEAP2 is primarily expressed in the prostate. In addition, significant levels of expression are found only in the ovaries. Expression in other tissues is very low, so STEAP2 is unlikely to have functional significance in these tissues.

The Function of STEAP2 Membrane Protein

STEAP2 can promote prostate cancer cell proliferation and regulate several genes involved in the cell cycle, leading to partial cell cycle arrest in G0-G1 phase. This proliferative activity of STEAP2 appears to be coordinated by the activation of the extracellular signal-regulated kinase (ERK) pathway. STEAP2 is highly expressed in metastatic cancer cell lines, so it must play a role in promoting the invasion of cancer cells into the local microenvironment, leading to tumor progression. Furthermore, STEAP2 is a survival factor in prostate cancer cells because its knockdown results in increased apoptosis in LNCaP cells. The role of STEAP2 in the apoptotic pathway is unclear, although exogenous apoptotic pathways may be possible due to the localization of STEAP2 on the cell membrane. Under normal conditions, extracellular signals activate receptors on the cell surface and trigger a signaling cascade that leads to the formation of a death-inducing signaling complex (DISC) that promotes apoptosis. Therefore, STEAP2 may inhibit the exogenous apoptotic pathway and may reduce DISC stability.

Fig.1 Schematic representation of STEAP2 protein structure, cell localization and physiological functions. (Gomes, 2012)

Application of STEAP2 Membrane Protein Literature

1. Hasegawa H., et al. Membrane cholesterol modulates STEAP2 conformation during dynamic intracellular trafficking processes leading to broad subcellular distribution. Experimental Cell Research. 2018, 27. PubMed ID:29940176
   
   

   This article finds that metal reductase activity of STEAP2 is not detected, indicating that its enzymatic function is inhibited on the plasma membrane and the conformational regulation of STEAP2 by local membrane cholesterol content could serve as a potential mechanism for regulating STEAP2 function in a compartmentally restricted manner.

2. Burnell S.E.A., et al. STEAP2 Knockdown Reduces the Invasive Potential of Prostate Cancer Cells. Scientific Reports. 2018, 8(1):6252. PubMed ID:29674723
   
   

   This article suggests that STEAP2 drives the characteristics of invasive prostate cancer by promoting cell proliferation, migration and invasion, and significantly affects the transcriptional profile of 10 genes underlying the metastatic cascade.

3. Whiteland H., et al. A role for STEAP2 in prostate cancer progression. Clinical & Experimental Metastasis. 2014, 31(8):909-20. PubMed ID:25248617
   
   

   This article finds that the overexpression of STEAP2 results in an additional ability to migrate and invade of normal prostate cells, suggesting that STEAP2 expression may be a key molecule driving prostate cancer cell invasion.

4. Porkka K.P., et al.Cloning and Characterization of a Novel Six-Transmembrane Protein STEAP2, Expressed in Normal and Malignant Prostate. Laboratory investigation; a journal of technical methods and pathology. 2002, 82(11):1573-82. PubMed ID:12429817
   
   

   This article reveals that the expression of STEAP2 in untreated primary and hormone-refractory prostate cancer is significantly higher than that of benign prostatic hyperplasia, suggesting that it may be involved in the development of prostate cancer.

5. Vaghjiani R.J., et al.Six-transmembrane epithelial antigen of the prostate (STEAP1 and STEAP2)-differentially expressed by murine and human mesenchymal stem cells. Tissue Eng Part A. 2009, 15(8):2073-83. PubMed ID:19196137
   
   

   This article suggests that all mesenchymal stem cell clones express differentially high levels of prostate six transmembrane epithelial antigens (STEAP1 and STEAP2).

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Reference

1. Gomes I M, et al. (2012). STEAP proteins: from structure to applications in cancer therapy. Molecular Cancer Research. 10(5):573-587.

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