STEAP1 Inhibits Breast Cancer Metastasis and Is Associated With Epithelial-Mesenchymal Transition Procession

Six-transmembrane epithelial antigen of prostate 1 (STEAP1) is a cell surface antigen overexpressed in multiple cancers and is associated with malignancy and disease prognosis. The aims of this study were to evaluate STEAP1 expression in breast cancer and to determine the mechanisms involved.

STEAP1 expression was compared in normal breast tissue (n = 40), benign fibroadenoma (n = 52), and primary breast cancer (n = 211) using immunohistochemistry. Quantitative real-time polymerase chain reaction, Western blot analysis, and immunocytochemistry were used to evaluate STEAP1 expression in 3 breast cancer cell lines and in a normal mammary epithelial cell line. STEAP1 expression and its prognostic value in breast cancer were verified using the Oncomine and Kaplan-Meier Plotter databases. Transfection of cells to up-regulate or knock down STEAP1 expression was used to determine the effect of STEAP1 on cell invasion and proliferation, and to evaluate its relationship to epithelial-mesenchymal transition (EMT) progression.

STEAP1 expression was lower in breast cancers cells, and low expression was associated with a malignant phenotype and poor prognosis. Analysis of public databases supported our conclusions. Knockdown of STEAP1 expression enhanced cellular invasion and migration abilities, increased expression of EMT-related genes MMP2, MMP9, MMP13, VIM, and CDH2, and decreased CDH1 expression. Enhanced STEAP1 expression significantly inhibited cellular invasion and migration abilities, decreased expression of the EMT-related genes, and increased CDH1 expression. Up-regulation or knockdown of STEAP1 had little effect on cellular proliferation.

STEAP1 was down-regulated in breast cancer, inhibited metastasis of breast cancer, and hampered the levels of EMT markers, which thus implicated STEAP1 in the suppression of EMT.