STEAP2 Knockdown Reduces the Invasive Potential of Prostate Cancer Cells

Abstract

Six-transmembrane epithelial antigen of the prostate-2 (STEAP2) expression is increased in prostate cancer when compared to normal prostate, suggesting STEAP2 may drive prostate cancer progression. This study aimed to establish the functional role of STEAP2 in prostate tumourigenesis and evaluate if its knockdown resulted in reduced invasive potential of prostate cancer cells. PC3 and LNCaP cells were transfected with STEAP2 siRNA and proliferation, migration, invasion and gene expression analyses were performed. STEAP2 immunohistochemistry was applied to assess the protein expression and localisation according to Gleason score in 164 prostate cancer patients. Invasion significantly decreased in both cell lines following STEAP2 knockdown. PC3 proliferation and migration capacity significantly reduced, while LNCaP cell morphology and growth characteristics were altered. Additionally, STEAP2 downstream targets associated with driving invasion were identified as MMP3, MMP10, MMP13, FGFR4, IL1β, KiSS1 and SERPINE1 in PC3 cells and, MMP7 in LNCaP cells, with CD82 altered in both. In patient tissues, STEAP2 expression was significantly increased in prostate cancer samples and this significantly correlated with Gleason score. These data demonstrate that STEAP2 drives aggressive prostate cancer traits by promoting proliferation, migration and invasion and significantly influencing the transcriptional profile of ten genes underlying the metastatic cascade.

Silencing of ELK3 Induces S-M Phase Arrest and Apoptosis and Upregulates SERPINE1 Expression Reducing Migration in Prostate Cancer Cells

“…Furthermore, we demonstrated that knockdown of ELK3 inhibited migration of DU145 cells in vitro (Figure 1(d)), which may partly due to upregulation of SERPINE1 via activation of AKT (Figure 4). SERPINE1 is a suppressor of cell migration [21,22] and its upregulation can reduce the invasive potential of PCa cells [23]. In this study, the silence of ELK3 increased SERPINE1 expression, indicating that ELK3 may play a negative role in the expression of SERPINE1 in PCa cells.…”

“…Studies have demonstrated that SERPINE1 prevents invasion of cancer cells by inhibiting uPA protease activity [22]. Moreover, six transmembrane epithelial antigen of the prostate 2 (STEAP2) knockdown, accompanied by SERPINE1 upregulation, can reduce the invasive potential of PCa cells [23]. Silencing of deleted in liver cancer 1 protein (DLC1) upregulates PAI-1 expression and reduces migration in normal prostate cells [24].…”

Recurrence-Associated Multi-RNA Signature to Predict Disease-Free Survival for Ovarian Cancer Patients

“…e roles of STEAP2 in OvCa may be similar to prostate cancer in which STEAP2 was observed to be upregulated and associated with advanced stage and Gleason score [37,38]. e overexpression of STEAP2 induced the normal prostate cells to gain an ability to migrate and invade [36] while the knockdown of STEAP2 significantly reduced proliferation and migration of prostate cancer cells [39]. However, no study was performed to verify the interaction between miR-186-STEAP2 and TM4SF1-AS1, which may be the direction of our future search.…”

Targeted Radionuclide Therapy of Prostate Cancer—From Basic Research to Clinical Perspectives

“…STEAP2 has been detected in androgen receptor (AR)-negative and (AR)-sensitive prostate cancer cell lines [52,53]. Moreover, recent evidence has demonstrated up-regulation of STEAP2 protein within prostate cancers compared to normal glands [54].…”