STEAP3, also known as Six-Transmembrane Epithelial Antigen of Prostate 3, TSAP6, or dudulin-2, is a metal reductase located on the plasma membrane close to the nucleus and vesicles [4,7]. It is involved in iron regulation [6] and has been associated with multiple biological processes and disease-related pathways. Its dysregulation has been linked to various diseases, highlighting its importance in understanding disease mechanisms [1-10]. Genetic models, especially gene knockout (KO) or conditional knockout (CKO) mouse models, can be valuable for studying its functions.

In cancer research, STEAP3 has diverse effects. In ovarian cancer, knockdown of STEAP3 reduced cell proliferation, migration, and induced ferroptosis through the p53/SLC7A11 pathway [2]. In colon cancer, it promotes cell proliferation and migration, and its knockdown inhibits these processes while down-regulating H3K27ac expression [3]. In glioma, high STEAP3 expression is related to shorter survival, and it promotes glioma progression through regulating the immune microenvironment and the PI3K-AKT pathway [4]. In renal cell carcinoma, knockdown of STEAP3 makes the cells more sensitive to ferroptosis via the p53/xCT pathway [5]. In hepatocellular carcinoma, nuclear STEAP3 promotes cancer cell proliferation by facilitating nuclear trafficking of EGFR to enhance RAC1-ERK-STAT3 signaling [7]. In colorectal cancer, hypoxia-induced lncRNA STEAP3-AS1 upregulates STEAP3 protein expression, which in turn promotes cancer progression through the Wnt/β-catenin signaling pathway [1].

In summary, STEAP3 plays crucial roles in multiple biological processes, especially in cancer development. KO/CKO mouse models would potentially further clarify its functions in these disease contexts, helping to understand the underlying mechanisms of diseases related to STEAP3 dysregulation, such as various cancers, and may provide new targets for therapeutic intervention.

References:

1. Zhou, Li, Jiang, Jingwen, Huang, Zhao, Chen, Hai-Ning, Huang, Canhua. 2022. Hypoxia-induced lncRNA STEAP3-AS1 activates Wnt/β-catenin signaling to promote colorectal cancer progression by preventing m6A-mediated degradation of STEAP3 mRNA. In Molecular cancer, 21, 168. doi:10.1186/s12943-022-01638-1. https://pubmed.ncbi.nlm.nih.gov/35986274/

2. Han, Yi, Fu, Lei, Kong, Yan, Huang, Liying, Zhang, Hualing. 2024. STEAP3 Affects Ovarian Cancer Progression by Regulating Ferroptosis through the p53/SLC7A11 Pathway. In Mediators of inflammation, 2024, 4048527. doi:10.1155/2024/4048527. https://pubmed.ncbi.nlm.nih.gov/38440354/

3. Lv, Jinjuan, Liu, Xiaoqian, Sun, Zhiwei, Ren, Shuangyi, Zuo, Yunfei. 2024. STEAP3 promotes colon cancer cell proliferation and migration via regulating histone acetylation. In Human genetics, 143, 343-355. doi:10.1007/s00439-024-02646-5. https://pubmed.ncbi.nlm.nih.gov/38480539/

4. Song, Zihan, Zhao, Zijun, Zhu, Siyu, Wang, Yizheng, Zhao, Zongmao. . STEAP3 is a prognostic biomarker that promotes glioma progression by regulating immune microenvironment and PI3K-AKT pathway. In Cancer biomarkers : section A of Disease markers, 38, 505-522. doi:10.3233/CBM-230217. https://pubmed.ncbi.nlm.nih.gov/37980651/

5. Ye, Cheng Lin, Du, Yang, Yu, Xi, Zheng, Yong Fa, Liu, Xiu Heng. . STEAP3 Affects Ferroptosis and Progression of Renal Cell Carcinoma Through the p53/xCT Pathway. In Technology in cancer research & treatment, 21, 15330338221078728. doi:10.1177/15330338221078728. https://pubmed.ncbi.nlm.nih.gov/35275508/

6. Zhang, Wenhua, Xie, Meng, Huang, Qiang, Sun, Xiaoli, Li, Conghui. 2024. STEAP3 is a potential preliminary prognostic biomarker of glioblastoma. In Scientific reports, 14, 30994. doi:10.1038/s41598-024-82145-9. https://pubmed.ncbi.nlm.nih.gov/39730631/

7. Wang, Li-Li, Luo, Jie, He, Zhang-Hai, Xie, Dan, Cai, Mu-Yan. 2021. STEAP3 promotes cancer cell proliferation by facilitating nuclear trafficking of EGFR to enhance RAC1-ERK-STAT3 signaling in hepatocellular carcinoma. In Cell death & disease, 12, 1052. doi:10.1038/s41419-021-04329-9. https://pubmed.ncbi.nlm.nih.gov/34741044/