Six-Transmembrane Epithelial Antigen of Prostate 3 Predicts Poor Prognosis and Promotes Glioblastoma Growth and Invasion

Mingzhi Han, Ran Xu, Shuai Wang, Ning Yang, Shilei Ni, Qing Zhang, Yangyang Xu, Xin Zhang, Chao Zhang, Yuzhen Wei, Jianxiong Ji, Bin Huang, Di Zhang, Anjing Chen, Wenjie Li, Rolf Bjerkvig, Xingang Li*, Jian Wang

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

45 Citations (Scopus)

Abstract

Recent evidence suggests that dysregulation of iron regulatory factors may play essential roles in cancer pathophysiology. Six-transmembrane epithelial antigen of prostate 3 (STEAP3) is a metalloreductase, which is vital for cellular iron uptake and homeostasis. However, the clinical significance and function of STEAP3 in the development of human gliomas remain unclear. Through analysis of publicly available databases, we found that STEAP3 was highly expressed in malignant gliomas, especially in the mesenchymal glioma molecular subtype and isocitrate dehydrogenase 1/2 (IDH1/2) wild-type gliomas. Expression levels of STEAP3 in gliomas correlated inversely with patient overall survival (OS) and served as an independent prognostic marker by multivariate Cox regression analysis. In functional assays performed with RNA knockdown, loss of STEAP3 attenuated aggressive phenotypes in glioma cells, including cell proliferation, invasion, and sphere formation in vitro and tumor growth in vivo. Finally, STEAP3 drives these activities by inducing mesenchymal transition, promoting transferrin receptor (TfR) expression, and activating STAT3-FoxM1 axis signaling. Taken together, these results indicate that STEAP3 functions as an oncogenic mediator in glioma progression and is thus a potential therapeutic target for the treatment of the disease.

Original languageEnglish
Pages (from-to)543-554
Number of pages12
JournalNeoplasia
Volume20
Issue number6
DOIs
Publication statusPublished - Jun 2018
Externally publishedYes

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