TRIB1 supports prostate tumorigenesis and tumor-propagating cell survival by regulation of endoplasmic reticulum chaperone expression

摘要: Endocrine therapy is the standard treatment for advanced prostate cancer; however, relapse occurs in most patients with few options available after recurrence. To overcome this therapeutic hurdle, identification of new molecular targets a critical issue. The capability to proliferate three-dimensional (3D) conditions characteristic property cancer cells. Therefore, factors that regulate 3D growth are considered rational therapy. Here, we applied functional genomic approach spheroid cell culture model and identified TRIB1, member Trib family serine/threonine kinase-like proteins, as an essential factor survival. RNAi-mediated silencing TRIB1 suppressed selectively under conditions. This effect was rescued by ectopic expression RNAi-resistant exogene. Gene signature-based analysis revealed related endoplasmic reticulum (ER) pathways required ER chaperone GRP78, which tumorigenesis. Of note, GRP78 expressed preferentially subpopulation cells possess tumor-propagating potential, these were highly sensitive depletion. In xenograft human cancer, depletion strongly inhibited tumor formation. Supporting observations, documented frequent overexpression clinical specimens cancer. Overall, our results indicated TRIB1-ER axis drives tumorigenesis survival