Glycolytic reprogramming through PCK2 regulates tumor initiation of prostate cancer cells

Jiangsha Zhao, Jieran Li, Teresa W.M. Fan, Steven X. Hou

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


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.

Original languageEnglish
Pages (from-to)83602-83618
Number of pages17
Issue number48
StatePublished - 2017

Bibliographical note

Funding Information:
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).

Publisher Copyright:
© Zhao et al.


  • Cancer
  • Glucose metabolism
  • Phosphoenolpyruvate carboxykinase isoform 2
  • Prostate
  • Tumorigenicity

ASJC Scopus subject areas

  • Oncology


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