TY - JOUR
T1 - Six-Transmembrane Epithelial Antigen of Prostate 3 Predicts Poor Prognosis and Promotes Glioblastoma Growth and Invasion
AU - Han, Mingzhi
AU - Xu, Ran
AU - Wang, Shuai
AU - Yang, Ning
AU - Ni, Shilei
AU - Zhang, Qing
AU - Xu, Yangyang
AU - Zhang, Xin
AU - Zhang, Chao
AU - Wei, Yuzhen
AU - Ji, Jianxiong
AU - Huang, Bin
AU - Zhang, Di
AU - Chen, Anjing
AU - Li, Wenjie
AU - Bjerkvig, Rolf
AU - Li, Xingang
AU - Wang, Jian
N1 - Publisher Copyright:
© 2018 The Authors
PY - 2018/6
Y1 - 2018/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85046713025&partnerID=8YFLogxK
U2 - 10.1016/j.neo.2018.04.002
DO - 10.1016/j.neo.2018.04.002
M3 - Article
C2 - 29730475
AN - SCOPUS:85046713025
SN - 1522-8002
VL - 20
SP - 543
EP - 554
JO - Neoplasia
JF - Neoplasia
IS - 6
ER -