Knockdown of STEAP1 inhibits cell growth and induces apoptosis in LNCaP prostate cancer cells counteracting the effect of androgens

Abstract

Six transmembrane epithelial antigen of the prostate 1 (STEAP1) is overexpressed in numerous types of tumors, especially in prostate cancer. STEAP1 is located in the plasma membrane of epithelial cells and may play an important role in inter- and intracellular communication. Several studies suggest STEAP1 as a potential biomarker and an immunotherapeutic target for prostate cancer. However, the role of STEAP1 in cell proliferation and apoptosis remains unclear. Therefore, the role of STEAP1 in prostate cancer cells proliferation and apoptosis was determined by inducing STEAP1 gene knockdown in LNCaP cells. In addition, the effect of DHT on the proliferation of LNCaP cells knocked down for STEAP1 gene was evaluated. Our results demonstrated that silencing the STEAP1 gene reduces LNCaP cell viability and proliferation, while inducing apoptosis. In addition, we showed that the cellular and molecular effects of STEAP1 gene knockdown may be independent of DHT treatment, and blocking STEAP1 may reveal to be an appropriate strategy to activate apoptosis in cancer cells, as well as to prevent the proliferative and anti-apoptotic effects of DHT in prostate cancer.

The Tumor Suppressive Roles and Prognostic Values of STEAP Family Members in Breast Cancer

“…This study expanded the knowledge of STEAPs in breast cancer and revealed the potentials of STEAPs for the therapy targets and prognostic biomarkers in breast cancer. It was proved that the expression of STEAP1 in prostate cancer is significantly increased, and silencing STEAP1 expression can inhibit the proliferation of prostate cancer cells and promote apoptosis [10]. Furthermore, the upregulation of STEAP1 has been also detected in lung, gastric, colorectal, renal, and bladder cancer [28][29][30][31].…”

“…It was proved that the expression of STEAP1 in prostate cancer is significantly increased, and silencing STEAP1 expression can inhibit the proliferation of prostate cancer cells and promote apoptosis [ 10 ]. Furthermore, the upregulation of STEAP1 has been also detected in lung, gastric, colorectal, renal, and bladder cancer [ 28 – 31 ].…”

“…Previous evidence reveals that STEAP1 is aberrantly high expressed in prostate cancer and predicted as a prostate-specific cell-surface antigen [ 9 ]. The subsequent identification of other STEAPs promoted the investigation of their normal and pathological function in different diseases, especially in cancers [ 10 – 14 ]. Recently, Sikkeland et al systematically reviewed the expression levels of STEAPs in normal tissues and disease states and reported the diverse role of STEAPs in normal and different pathological tissues, revealing that only STEAP3 was reported to be highly expressed in the mammary gland [ 15 ].…”

The Usefulness of STEAP Proteins in Prostate Cancer Clinical Practice

“…Humanized variant of anti-STEAP1 monoclonal antibody (mAb 120.545) is currently used in prostate cancer clinical trials as an antibody-drug conjugate (DSTP3086S) (24), and as a radiolabeled antibody (89Zr-DFO-MSTP2109A) for PET imaging (24,25). In addition, several studies exploring the role of STEAP1 in cancer cells showed that its overexpression inhibits apoptosis, enhances cell proliferation and invasion, and induces epithelial to mesenchymal transition, ultimately contributing to tumor progression and aggressiveness (4,5,(26)(27)(28)(29)(30).…”

Advances in Targeting Cancer-Associated Genes by Designed siRNA in Prostate Cancer

“…Results demonstrated that knockdown of α5-nAChR causes reduced levels of phospho-AKT and phospho-ERK1/2, followed by a significant decrease in cell migration and invasion and an induction of apoptosis, indicating the impact of α5-nAChR on the proliferation and invasion of human PCa cells and the importance of its silencing in PCa treatment [43]. Finally, six transmembrane epithelial antigens of the prostate 1 (STEAP1) was shown to be overexpressed in various types of tumors, particularly in PCa, and knockdown of STEAP1 in LNCaP cells by siRNA decreases cell viability and proliferation, whilst promoting apoptosis [44]. All together, these data suggest that cell membrane proteins could serve as appropriate targets for PCa treatment.…”