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Mol. Cells 2013; 35(4): 335-341

Published online April 30, 2013

https://doi.org/10.1007/s10059-013-2319-4

© The Korean Society for Molecular and Cellular Biology

Metabolic Signature Genes Associated with Susceptibility to Pyruvate Kinase, Muscle Type 2 Gene Ablation in Cancer Cells

Yuri Jung, Ye Jin Jang1, Min Ho Kang, Young Soo Park, Su Jin Oh, Dong Chul Lee, Zhi Xie, Hyang-Sook Yoo, Kyung Chan Park, and Young Il Yeom

1Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea, 2Department of Functional Genomics, University of Science and Technology, Daejeon 305-350, Korea, 3Pfizer Global Research and Development, 10770 Science Center Drive, San Diego, California 92121, USA

Received: December 6, 2013; Revised: February 28, 2013; Accepted: March 4, 2013

Abstract

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).

Keywords glycolysis, glycolysis-dependent, lactate, PKM2, SLC16A3

Article

Research Article

Mol. Cells 2013; 35(4): 335-341

Published online April 30, 2013 https://doi.org/10.1007/s10059-013-2319-4

Copyright © The Korean Society for Molecular and Cellular Biology.

Metabolic Signature Genes Associated with Susceptibility to Pyruvate Kinase, Muscle Type 2 Gene Ablation in Cancer Cells

Yuri Jung, Ye Jin Jang1, Min Ho Kang, Young Soo Park, Su Jin Oh, Dong Chul Lee, Zhi Xie, Hyang-Sook Yoo, Kyung Chan Park, and Young Il Yeom

1Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea, 2Department of Functional Genomics, University of Science and Technology, Daejeon 305-350, Korea, 3Pfizer Global Research and Development, 10770 Science Center Drive, San Diego, California 92121, USA

Received: December 6, 2013; Revised: February 28, 2013; Accepted: March 4, 2013

Abstract

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).

Keywords: glycolysis, glycolysis-dependent, lactate, PKM2, SLC16A3

Mol. Cells
May 31, 2022 Vol.45 No.5, pp. 273~352
COVER PICTURE
Fe2+ ion depletion-induced expression of BΔGFP at the early stage of leaf development (Choi et al., pp. 294-305).

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