Tumor-initiating cells (TICs) play important roles in tumor progression and metastasis. Identifying the factors regulating TICs may open new avenues in cancer therapy. Here, we show that TIC-enriched prostate cancer cell clones use more glucose and secrete more lactate than TIC-low clones. We determined that elevated levels of phosphoenolpyruvate carboxykinase isoform 2 (PCK2) are critical for the metabolic switch and the maintenance of TICs in prostate cancer. Information from prostate cancer patient databases revealed that higher PCK2 levels correlated with more aggressive tumors and lower survival rates. PCK2 knockdown resulted in low TIC numbers, increased cytosolic acetyl-CoA and cellular protein acetylation. Our data suggest PCK2 promotes tumor initiation by lowering acetyl-CoA level through reducing the mitochondrial tricarboxylic acid (TCA) cycle. Thus, PCK2 is a potential therapeutic target for aggressive prostate tumors.
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This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute (to SXH) and NIH grant numbers 1U24DK097215-01A1, 1P01CA163223-01A1, 1R01ES022191-01, and 3R01ES022191-04S1 (to TWMF).
Zhao, Jiangsha; Li, Jieran; Fan, Teresa W.M.; and Hou, Steven X., "Glycolytic Reprogramming Through PCK2 Regulates Tumor Initiation of Prostate Cancer Cells" (2017). Toxicology and Cancer Biology Faculty Publications. 68.