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.
Document Type
Article
Publication Date
10-13-2017
Digital Object Identifier (DOI)
https://doi.org/10.18632/oncotarget.18787
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).
Related Content
Repository Citation
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.
https://uknowledge.uky.edu/toxicology_facpub/68
Supplementary File
Notes/Citation Information
Published in Oncotarget, v. 8, issue 48, p. 83602-83618.
© 2017 Zhao et al.
This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.