A bioinformatics screen identifies TCF19 as an aggressiveness-sustaining gene in prostate cancer
Prostate cancer is a prevalent tumor type that, despite being highly curable, progresses to metastatic disease in a fraction of patients, thus accounting for more than 350?000 annual deaths worldwide. In turn, uncovering the molecular insights of metastatic disease is instrumental in improving the survival rate of prostate cancer patients. By means of gene expression meta-analysis in multiple prostate cancer patient cohorts, we identified a set of genes that are differentially expressed in aggressive prostate cancer. Transcription factor 19 (TCF19) stood out as an unprecedented epithelial gene upregulated in metastatic disease, with prognostic potential and negatively associated with the activity of the androgen receptor. By combining computational and empirical approaches, our data revealed that TCF19 is required for full metastatic capacity, and its depletion influences core cancer-related processes, such as tumor growth and vascular permeability, supporting the role of this gene in the dissemination of prostate tumor cells. Overall design: GFP-Luc PC3 cells expressing stable shRNAs against Scramble or TCF19 were injected into the ventral lobe of the prostates of immune-deficient nude mice. Prostate primary tumors were collected after 19 days and processed for transcriptomics analysis. 6 tumors per group were collected.