Six‐transmembrane epithelial antigen of the prostate 1 is associated with tumor invasion and migration in endometrial carcinomas

Abstract

Six-transmembrane epithelial antigen of the prostate 1 (STEAP1), a member of the STEAP family, is a general tumor antigen. However, no information has been available to date regarding the function of STEAP1 in the progression of endometrial carcinoma. In this study, we used in vitro and in vivo strategies to prove that STEAP1 plays an important role in the progression of endometrial carcinoma. Immunohistochemistry, immunocytochemistry, quantitative reverse transcription polymerase chain reaction (RT-qPCR), and Western blot analysis were used to detect the expression of STEAP1 in normal endometrial cells and endometrial cancer cell lines. The progression of the cell cycle, plate clone formation assay, and transwell migration and invasion assays were performed to examine the effects of STEAP1 on cell proliferation, clonogenicity, migration, and their invasive capacity. In addition, we confirmed that STEAP1 was tightly correlated with the development of tumor in vivo. The relationship between epithelial to mesenchymal transition (EMT) and STEAP1 expression was evaluated by RT-qPCR and Western blot analysis. Matrix metalloproteinase (MMP) zymography assay was used to detect the activities of MMP2 and MMP9. STEAP1 was restrictively expressed in endometrial carcinoma and downregulation of the STEAP1 gene increased proliferation and clonogenicity, as well as promoted cell migration, invasion, and the progress of EMT. STEAP1 is downregulated in endometrial carcinoma and can restrict migration and invasion of endometrial carcinoma cells. Overall, STEAP1 may be an ideal target for tumor therapy and diagnosis in the future. K E Y W O R D S endometrial carcinoma, epithelial to mesenchymal transition, invasion, migration, six-transmembrane epithelial antigen of the prostate 1A standard streptavidin-biotin-peroxidase staining procedure was used, wherein formalin-fixed, paraffin-embedded endometrial tissues were cut into 5-μm slices. After a series of processing steps, such as dewaxing in xylene, rehydration, and antigen retrieval, sections were incubated with the mouse anti-human STEAP1 monoclonal antibody (ab117454; Abcam) at a dilution of 1﹕200 . Six-transmembrane epithelial antigen of the prostate 1 is associated with tumor invasion and migration in endometrial carcinomas.

Evaluation of the Prognostic Value of STEAP1 in Lung Adenocarcinoma and Insights Into Its Potential Molecular Pathways via Bioinformatic Analysis

“…However, STEAP1 downregulation has been reported in endometrial carcinoma, and STEAP1 upregulation is associated with a better patient prognosis rather than STEAP1 downregulation (Sun et al, 2019). In contrast, some studies have indicated that STEAP1 upregulation is associated with reduced growth and migration of endometrial cancer cells (Sun et al, 2019). Furthermore, STEAP1 is reportedly upregulated in Ewing's tumor and colorectal cancer, and the prognosis of patients with high STEAP1 expression levels was better than that of patients with low expression levels (Grunewald et al, 2012c;Lee et al, 2016;Nakamura et al, 2019).…”

“…Targeting STEAP1 expression may potentially inhibit the proliferation of and induced apoptosis in prostate cancer cells (Gomes et al, 2014(Gomes et al, , 2018. However, STEAP1 downregulation has been reported in endometrial carcinoma, and STEAP1 upregulation is associated with a better patient prognosis rather than STEAP1 downregulation (Sun et al, 2019). In contrast, some studies have indicated that STEAP1 upregulation is associated with reduced growth and migration of endometrial cancer cells (Sun et al, 2019).…”

Comprehensive landscape of STEAP family functions and prognostic prediction value in glioblastoma

“…STEAP family was found to reduce the ferric iron to ferrous iron to increase cellular iron uptake (Ohgami et al, 2006). In addition, the STEAP family interacted with various genes involving in the cell cycle and thus regulated cancer cell growth and proliferation (Qin et al, 2010; Sun et al, 2019; Wang et al, 2010).…”

Fusion Protein Vaccine Based on Ag85B and STEAP1 Induces a Protective Immune Response against Prostate Cancer

“…The STEAP1 protein is overexpressed in prostate, bladder, renal, breast, testicular, pancreatic, cervical, and ovarian cancer, making STEAP1 an attractive candidate for a wide range of cancer immunotherapies [ 15 , 29 , 30 , 31 , 32 , 33 ]. Previous studies have identified a H-2K b epitope STEAP1 186-193 (RSYRYKLL) [ 15 , 34 , 35 , 36 , 37 ].…”