Glucose Metabolic Remodeling through Phosphoenolpyruvate Carboxykinase Isoform 2 Regulates Prostate Cancer Cell Tumorigenicity

Patients with aggressive prostate cancer generally present with poor outcomes. Identifying the factors regulating prostate cancer aggressiveness may open new avenues in therapy. Specifically, information from prostate cancer patient databases revealed that higher phosphoenolpyruvate carboxykinase isoform 2 (PCK2) levels correlate with more aggressive tumors and lower survival rates. Herein, we show that high tumorigenic prostate cancer cell clones express high levels of PCK2. We found that elevated levels of PCK2 are critical for the glucose metabolic remodeling and the maintenance of tumor-initiating cells (TICs) in aggressive prostate cancer. Our data suggest that PCK2 promotes tumorigenicity by lowering acetyl-CoA levels through reducing the mitochondrial tricarboxylic acid (TCA) cycle. Thus, PCK2 is a potential therapeutic target for aggressive prostate cancer. 2 subclones have been isolated from DU145 cells. The epithelial like (EL) clone has a high tumorigenicity ability and enriched tumor initiating cells than mesenchymal like (ML) clone. Genes with differential expression pattern between these two clones were detected by gene micorarray.