| 2006 |
STEAP2, STEAP3, and STEAP4 are ferrireductases and cupric reductases that stimulate cellular uptake of both iron and copper in vitro; STEAP1, unlike the other family members, was not demonstrated to have these activities in this study (implicitly negative for STEAP1 ferrireductase/cupric reductase activity in this assay context). |
Functional expression studies, cellular iron/copper uptake assays |
Blood |
High |
16609065
|
| 1999 |
STEAP1 is a six-transmembrane protein localized at cell-cell junctions of the secretory epithelium of the prostate, consistent with a role as a channel or transporter protein at the plasma membrane. |
Immunohistochemistry, protein analysis of cancer cell lines, cDNA subtraction cloning |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
10588738
|
| 2015 |
The STEAP3 transmembrane domain binds a single b-type heme, FAD, and iron; STEAP3 functions as a homodimer using an intrasubunit electron transfer pathway through the single heme rather than an intersubunit pathway. The sequence motifs for FAD and metal binding in the transmembrane domain are conserved in STEAP1 (which lacks the N-terminal oxidoreductase domain), strongly suggesting STEAP1 harbors latent oxidoreductase activity. |
Biochemical characterization, mutagenesis, in vitro electron transfer assays, analysis of homodimer vs. domain-swapped dimer |
The Journal of biological chemistry |
High |
26205815
|
| 2016 |
Purified rabbit STEAP1 assembles as a homotrimer and forms a heterotrimer when co-expressed with STEAP2. Each STEAP1 protomer binds one b-type heme with histidine axial ligands. In its ferrous state, STEAP1 reduces Fe3+ and Cu2+ complexes and reacts with O2 via an outer-sphere redox mechanism. STEAP1 retains low-affinity FAD binding (KD ~30 µM). Kinetics are biphasic, consistent with heme heterogeneity. |
Protein purification at milligram scale, spectroscopic characterization (EPR, UV-vis), stopped-flow kinetics, co-expression experiments |
Biochemistry |
High |
27792302
|
| 2020 |
Cryo-EM structure of trimeric human STEAP1 at ~3.0 Å reveals a reductase-like transmembrane conformation. STEAP1 lacks an intracellular NADPH-binding domain and does not exhibit standalone cellular ferric reductase activity. However, STEAP1 promotes iron(III) reduction when fused to the intracellular NADPH-binding domain of STEAP4, demonstrating it can function as a ferric reductase within STEAP heterotrimers. The Fab of antibody mAb120.545 binds the extracellular helices of STEAP1. |
Cryo-electron microscopy (3.0 Å resolution), enzymatic assays in human cells using STEAP1-STEAP4 fusion constructs |
The Journal of biological chemistry |
High |
32409586
|
| 2020 |
The STEAP/NOX ferric reductase superfamily shares a conserved four-helical transmembrane domain with an hourglass shape; within this shared scaffold, STEAP enzymes use FAD (bound to a cytoplasmic F420H2:NADP+-like domain) whereas NOX uses an inner heme, representing a cofactor swap at a topologically equivalent site. The extracellular heme mediates substrate reduction (iron/copper for STEAPs, O2 for NOX). |
Structural comparison of cryo-EM structures of NOX and STEAP enzymes |
Accounts of chemical research |
Medium |
32815713
|
| 2023 |
STEAP1 can be reduced by exogenous reduced FAD or soluble cytochrome b5 reductase acting as a surrogate oxidoreductase domain, providing the first direct evidence that STEAP1 can support a cross-membrane electron transfer chain. FAD reduced by STEAP2 can be utilized by STEAP1, indicating that FAD is diffusible between STEAP subunits rather than remaining permanently bound to STEAP2. Cryo-EM structure of human STEAP2 in complex with NADP+ and FAD (3.2 Å) confirms cofactor binding similar to STEAP4. |
In vitro electron transfer assays with purified proteins, cryo-EM (3.2 Å), FAD transfer experiments between STEAP1 and STEAP2 |
eLife |
High |
37983176
|
| 2011 |
STEAP1 knockdown in Ewing tumor cells reduces proliferation, anchorage-independent colony formation, and invasion in vitro, and decreases tumor growth and metastasis in xenografts in vivo. Transcriptome and proteome analyses show STEAP1 expression correlates with oxidative stress responses and elevated reactive oxygen species (ROS), which in turn regulate redox-sensitive and pro-invasive genes. STEAP1 expression is regulated by the EWS/FLI1 fusion oncoprotein. |
RNA interference (siRNA/shRNA), in vitro invasion/colony assays, xenograft mouse models, transcriptome and proteome analyses, ROS measurement |
Molecular cancer research : MCR |
High |
22080479
|
| 2018 |
STEAP1 gene knockdown in LNCaP prostate cancer cells reduces cell viability and proliferation while inducing apoptosis. The pro-survival and anti-apoptotic effects of dihydrotestosterone (DHT) are not dependent on STEAP1, as STEAP1 knockdown effects on apoptosis and proliferation were independent of DHT treatment. |
siRNA knockdown, cell viability assays, flow cytometry for apoptosis, DHT treatment |
Medical oncology (Northwood, London, England) |
Medium |
29464393
|
| 2008 |
STEAP1 transcription is down-regulated by 17β-estradiol (E2) in rat mammary gland and in MCF-7 breast cancer cells. The mechanism of E2-mediated STEAP1 repression in MCF-7 cells is mediated through membrane-bound ERα (mbERα). |
In vivo rat mammary gland E2 treatment, MCF-7 cell hormone treatment, mechanistic studies with membrane-bound ERα |
Endocrine |
Medium |
18958632
|
| 2020 |
STEAP1 promotes metastasis and epithelial-mesenchymal transition (EMT) in lung adenocarcinoma cells via the JAK2/STAT3 signaling pathway. Knockdown of STEAP1 suppressed proliferation, migration, and invasion; these effects were phenocopied by a STAT3 inhibitor (AZD1480), placing STEAP1 upstream of JAK2/STAT3 in this cancer context. |
siRNA knockdown, CCK8/EdU/wound healing/transwell assays, Western blot, pharmacological STAT3 inhibition |
Bioscience reports |
Medium |
32515474
|
| 2018 |
STEAP1 regulates peritoneal metastasis-related tumorigenesis in gastric cancer cells; RNAi-mediated silencing of STEAP1 inhibits proliferation, migration, invasion, and in vivo tumorigenesis, and increases sensitivity to docetaxel. STEAP1 was identified as the most translationally upregulated gene product in metastatic vs. non-metastatic gastric cancer cells by polysome profiling. |
Polysome profiling, siRNA/shRNA knockdown, overexpression plasmid, MTT/migration/invasion assays, xenograft mouse model |
Frontiers in physiology |
Medium |
30246786
|
| 2020 |
Phosphorylated eIF4E controls cap-dependent translational upregulation of STEAP1 in gastric cancer cells undergoing peritoneal metastasis. Chemical inhibition or genetic ablation of eIF4E phosphorylation reduces STEAP1 protein levels, placing phospho-eIF4E upstream of STEAP1 in the translational control pathway. |
Chemical inhibitors of eIF4E phosphorylation, genetic eIF4E knockout, translational reporter assays, Western blot |
Journal of Cancer |
Medium |
31949502
|
| 2020 |
STEAP1 promotes gastric cancer cell proliferation, migration, and invasion via activation of the AKT/FoxO1 pathway and epithelial-mesenchymal transformation (EMT). Both overexpression and knockdown experiments confirmed these effects in vitro and in xenograft mouse models. |
Overexpression plasmid, lentiviral shRNA, CCK-8, flow cytometry, colony formation, transwell and wound healing assays, Western blot, subcutaneous and intraperitoneal xenograft |
Journal of cellular and molecular medicine |
Medium |
33128353
|
| 2021 |
NKX2.2 is a transcriptional co-regulator of STEAP1 in Ewing's sarcoma. NKX2.2 binds to two sites in the STEAP1 promoter proximal to EWS/FLI1 binding sites and cooperatively upregulates STEAP1 expression together with EWS/FLI1. |
Chromatin immunoprecipitation (ChIP), single-molecule RNA imaging, biochemical and genetic studies, promoter analysis |
Cells |
Medium |
34073779
|
| 2022 |
EFEMP1 directly promotes STEAP1 expression in osteosarcoma cells; knockdown of STEAP1 in EFEMP1-overexpressing cells significantly inhibits invasion, EMT, and Wnt/β-catenin and TGF-β/Smad2/3 signaling, placing STEAP1 downstream of EFEMP1 in these pathways. Exogenous EFEMP1 fails to activate these pathways when STEAP1 is knocked down. |
Overexpression and knockdown constructs, IHC, RT-qPCR, Western blot, in vitro invasion assays, epistasis experiments |
Journal of bone oncology |
Medium |
36388640
|
| 2023 |
STEAP1 promotes ferroptosis in acute lung injury; inhibition of STEAP1 decreases ROS and MDA levels, increases Nrf2 and GSH levels, and affects the SLC7A11/GPX4 axis, suggesting STEAP1 modulates ferroptosis through this pathway. |
siRNA knockdown in HPMECs, LPS-induced ALI model, CLP mouse model, ROS/MDA/GSH/Fe2+ measurements, Western blot |
Molecular biology reports |
Medium |
37209327
|
| 2024 |
METTL14 and IGF2BP2 stabilize STEAP1 mRNA through m6A methylation modification. METTL14 silencing attenuates LPS-induced effects by decreasing STEAP1 expression. This m6A-dependent STEAP1 upregulation aggravates sepsis-induced acute lung injury. |
m6A RNA immunoprecipitation, dual-luciferase reporter assay, RNA immunoprecipitation, actinomycin D mRNA stability assay, siRNA knockdown, CLP rat model |
Shock (Augusta, Ga.) |
Medium |
39193903
|
| 2009 |
STEAP1 depletion by RNAi in human mesenchymal stem cells (MSCs) results in decreased cell adhesion to tissue culture plastic, implicating STEAP1 in cell adhesion in MSCs. |
RNAi knockdown in human bone marrow MSCs, cell adhesion assay |
Tissue engineering. Part A |
Low |
19196137
|
| 2018 |
A specific anti-STEAP1 scFv antibody binding to STEAP1 epitope significantly inhibits intercellular communication (dye transfer) between prostate cancer cells (PC3 and LNCaP) by ~80-90%, supporting STEAP1's role as a channel or transporter mediating gap junction-like intercellular communication. |
Phage library panning for scFv, ELISA, FACS, intercellular dye transfer (gap junction) assay |
Anti-cancer agents in medicinal chemistry |
Low |
29219059
|
| 2014 |
STEAP1 expression in prostate cancer is regulated by the androgen receptor (AR) in an AR-dependent manner in CWR22PC cells (in vitro and in vivo), demonstrated by ~66% decline in STEAP1 levels upon AR-targeted treatment monitored by 89Zr-immunoPET. |
89Zr-immunoPET imaging, in vitro and in vivo treatment with AR-targeting therapy, ELISA |
Journal of nuclear medicine : official publication, Society of Nuclear Medicine |
Medium |
25453051
|
| 2014 |
STEAP1 protein stability and mRNA stability differ between neoplastic (LNCaP) and non-neoplastic (PNT1A) prostate cells. Serum has opposite effects on STEAP1 stability in these two cell types, and in silico analysis predicts post-translational modifications including N-glycosylation, phosphorylation, and O-GlcNAcylation. |
mRNA and protein stability experiments, serum treatment, in silico PTM prediction |
Genes & cancer |
Low |
25053991
|
| 2021 |
STEAP1 is selectively packaged into small extracellular vesicles (sEVs) from prostate cancer cells irrespective of androgen receptor (AR) status and cellular STEAP1 expression levels, indicating a selective EV-loading mechanism for STEAP1. |
Androgen deprivation/AR inhibition in multiple cell lines, Western blot and nanoparticle tracking of sEVs, ex vivo analysis in genetically engineered mice |
Molecular cancer research : MCR |
Low |
40287951
|
| 2018 |
STEAP1 overexpression in breast cancer cells inhibits cellular invasion and migration and reduces EMT marker expression (MMP2, MMP9, MMP13, VIM, CDH2), while increasing CDH1. Knockdown has the opposite effects. STEAP1 had little effect on proliferation in breast cancer cells. |
Overexpression and knockdown in breast cancer cell lines, transwell invasion/migration, Western blot for EMT markers |
Clinical breast cancer |
Medium |
30253922
|
| 2026 |
STEAP1 overexpression in oral squamous cell carcinoma (OSCC) cells inhibits proliferation, migration, invasion, and reduces intracellular ROS levels. Mechanistically, STEAP1 overexpression upregulates E-cadherin, downregulates N-cadherin (inhibiting EMT), and decreases β-catenin, Axin2, c-Myc, and p-GSK3β/T-GSK3β ratio (inhibiting Wnt/β-catenin signaling). |
Plasmid overexpression in OSCC cell lines, CCK-8, scratch, Transwell assays, ROS measurement, Western blot |
Cancer medicine |
Low |
42046243
|
| 2023 |
Proteomic analysis following STEAP1 siRNA knockdown in LNCaP prostate cancer cells identified 526 differentially expressed proteins; downstream pathways affected include endocytosis, apoptosis, and metabolic pathways. STEAP1 silencing specifically induced up-regulation of cathepsin B, intersectin-1, and syntaxin 4, and down-regulation of HRas, PIK3C2A, and DIS3. |
siRNA knockdown, label-free LC-MS/MS proteomics (Orbitrap), immunoblotting |
Biochimica et biophysica acta. Molecular cell research |
Medium |
37315586
|