Research Papers:
Glycolytic reprogramming through PCK2 regulates tumor initiation of prostate cancer cells
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Abstract
Jiangsha Zhao1, Jieran Li2, Teresa W.M. Fan2 and Steven X. Hou1
1The Basic Research Laboratory, National Cancer Institute, National Institutes of Health Frederick, Frederick, MD 21702, USA
2Graduate Center of Toxicology and Cancer Biology, Center for Environmental and Systems Biochemistry, and Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA
Correspondence to:
Steven X. Hou, email: [email protected]
Keywords: cancer, glucose metabolism, phosphoenolpyruvate carboxykinase isoform 2, prostate, tumorigenicity
Received: April 04, 2017 Accepted: May 21, 2017 Published: June 28, 2017
ABSTRACT
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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PII: 18787