Journal
MOLECULES AND CELLS
Volume 35, Issue 4, Pages 335-341Publisher
KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
DOI: 10.1007/s10059-013-2319-4
Keywords
glycolysis; glycolysis-dependent; lactate; PKM2; SLC16A3
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Funding
- National Research Foundation (NRF)
- Ministry of Education and Science Technology of Korea (MEST) [2010-0010465, 2011-0028171]
- National R&D Program for Cancer Control from the Ministry of Health and Welfare of Korea (MHW) [0720050]
- Korea Research Institute of Bioscience and Biotechnology (KRIBB) Research Initiative Program
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Pyruvate kinase, muscle type 2 (PKM2), is a key factor in the aerobic glycolysis of cancer cells. In our experiments, liver cancer cell lines exhibited a range of sensitivity to PKM2 knockdown-mediated growth inhibition. We speculated that this differential sensitivity is attributable to the variable dependency on glycolysis for the growth of different cell lines. Transcriptome data revealed overexpression of a glucose transporter (GLUT3) and a lactate transporter (MCT4) genes in PKM2 knockdown-sensitive cells. PKM2 knockdown-resistant cells expressed high levels of the lactate dehydrogenase B (LDHB) and glycine decarboxylase (GLDC) genes. Concordant with the gene expression results, PKM2 knockdown-sensitive cells generated high levels of lactate. In addition, ATP production was significantly reduced in the PKM2 knockdown-sensitive cells treated with a glucose analog, indicative of dependency of their cellular energetics on lactate-producing glycolysis. The PKM2 knockdown-resistant cells were further subdivided into less glycolytic and more (glycolysis branch pathway-dependent) glycolytic groups. Our findings collectively support the utility of PKM2 as a therapeutic target for high lactate-producing glycolytic hepatocellular carcinoma (HCC).
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