TROAP Regulates Prostate Cancer Progression Via the WNT3/survivin Signalling Pathways

Prostate cancer (PCa) is one of the most commonly diagnosed malignancies, and 90% of advanced prostate cancer patients relapse after therapy. Trophinin associated protein (TROAP) is essential for centrosome integrity and proper bipolar organisation of spindle assembly during mitosis and plays an essential role in proliferation. We found that TROAP expression correlates with patient survival and speculated that it may be involved in PCa progression. The Oncomine database tool (http://www.oncomine.org) was used to analyse TROAP mRNA expression from microarray data, and patient survival analysis for target genes was performed using the PROGgeneV2 Database (http://watson.compbio.iupui.edu). Gene interference with lentivirus was used to silence TROAP expression in PCa cells and knockdown efficiency was detected by qRT-PCR and western blot analysis. Cell viability, colony formation, cell cycle and apoptosis were then assessed to determine the function of TROAP in PCa cells. Markers of cell cycle and apoptosis were tested by western blotting. The correlation between WNT3 or survivin expression and TROAP transcripts in prostate cancer tissues was analysed using GEPIA (http://gepia.cancer-pku.cn) and validated by western blotting. The in vivo role of TROAP was investigated using xenografts. This protein was overexpressed in PCa, and exhibited relatively higher expression in PCa cell lines, DU145 and 22Rv1. Importantly, analysing human cancer databases available from PROGgeneV2 showed that higher expression of TROAP is associated with shorter overall survival in prostate cancer patients. TROAP knockdown inhibited cell proliferation and led to cell cycle arrest at S phase in 22Rv1 and DU145 cells. Cell cycle arrest resulted in apoptosis in both cell lines via the cyclin A2-cyclin B1-caspase pathway. WNT3 and survivin expression levels were found to correlate with TROAP in PCa, and in vivo xenograft assays revealed that silencing of TROAP inhibited PCa tumour growth. Therefore, TROAP might represent a novel predictive marker to guide therapeutic intervention.