Six-Transmembrane Epithelial Antigen of Prostate 3 Predicts Poor Prognosis and Promotes Glioblastoma Growth and Invasion.
Six-Transmembrane Epithelial Antigen of Prostate 3 Predicts Poor Prognosis and Promotes Glioblastoma Growth and Invasion.
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前列腺六跨膜上皮抗原 3 预测不良预后并促进胶质母细胞瘤生长和侵袭
DOI：
10.1016/j.neo.2018.04.002
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发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Han M;Xu R;Wang S;Yang N;Ni S;Zhang Q;Xu Y;Zhang X;Zhang C;Wei Y;Ji J;Huang B;Zhang D;Chen A;Li W;Bjerkvig R;Li X;Wang J
最近的证据表明，铁调节因子的失调可能在癌症的病理生理学中发挥重要作用。前列腺六跨膜上皮抗原3（STEAP 3）是一种金属还原酶，对细胞铁的摄取和体内平衡至关重要。然而，STEAP 3在人类胶质瘤发展中的临床意义和功能仍不清楚。通过对公开数据库的分析，我们发现STEAP 3在恶性胶质瘤中高度表达，尤其是在间叶胶质瘤分子亚型和异柠檬酸脱氢酶1/2（IDH 1/2）野生型胶质瘤中。STEAP 3在胶质瘤中的表达水平与患者的总生存期（OS）呈负相关，并通过多变量考克斯回归分析作为独立的预后指标。在用RNA敲低进行的功能测定中，STEAP 3的缺失减弱了胶质瘤细胞中的侵袭性表型，包括体外细胞增殖、侵袭和球体形成以及体内肿瘤生长。最后，STEAP 3通过诱导间质转化、促进转铁蛋白受体（TfR）表达和激活STAT 3-FoxM 1轴信号传导来驱动这些活动。总之，这些结果表明STEAP 3在胶质瘤进展中作为致癌介质发挥作用，因此是治疗该疾病的潜在治疗靶点。
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.
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影响因子：
5.6
作者：
Lee CY;Shin S;Lee J;Seo HH;Lim KH;Kim H;Choi JW;Kim SW;Lee S;Lim S;Hwang KC
通讯作者：
Hwang KC
影响因子：
11.2
作者：
Song, Siyuan;Christova, Tania;Attisano, Liliana
通讯作者：
Attisano, Liliana
影响因子：
50.3
作者：
Phillips, HS;Kharbanda, S;Aldape, K
通讯作者：
Aldape, K
影响因子：
30.8
作者：
Ohgami, RS;Campagna, DR;Fleming, MD
通讯作者：
Fleming, MD
影响因子：
30.8
作者：
Fleming, MD;Trenor, CC;Andrews, NC
通讯作者：
Andrews, NC