Metabolic signature genes associated with susceptibility to pyruvate kinase, muscle type 2 gene ablation in cancer cells

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 variabl...

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Published in	Molecules and cells Vol. 35; no. 4; pp. 335 - 341
Main Authors	Jung, Yuri, Jang, Ye Jin, Kang, Min Ho, Park, Young Soo, Oh, Su Jin, Lee, Dong Chul, Xie, Zhi, Yoo, Hyang-Sook, Park, Kyung Chan, Yeom, Young Il
Format	Journal Article
Language	English
Published	Springer Korean Society for Molecular and Cellular Biology 01.04.2013 Korea Society for Molecular and Cellular Biology 한국분자세포생물학회
Subjects	Biochemistry Biomedical and Life Sciences Biomedicine Biotechnology Carcinoma, Hepatocellular - enzymology Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - metabolism Carcinoma, Hepatocellular - pathology Carrier Proteins - genetics Carrier Proteins - metabolism Cell Biology Cell Line, Tumor Cell Survival - physiology Gene Expression Gene Knockdown Techniques Glucose Transporter Type 3 - biosynthesis Glucose Transporter Type 3 - genetics Glycolysis Humans Lactic Acid - metabolism Life Sciences Liver Neoplasms - enzymology Liver Neoplasms - genetics Liver Neoplasms - metabolism Liver Neoplasms - pathology Membrane Proteins - deficiency Membrane Proteins - genetics Membrane Proteins - metabolism Research Article Thyroid Hormone-Binding Proteins Thyroid Hormones - deficiency Thyroid Hormones - genetics Thyroid Hormones - metabolism 생물학 glycolysis-dependent lactate PKM2 SLC16A3 glycolysis
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ISSN	1016-8478 0219-1032
DOI	10.1007/s10059-013-2319-4

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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).
AbstractList	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). 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). KCI Citation Count: 12 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).[PUBLICATION ABSTRACT]
Author	Lee, Dong Chul Xie, Zhi Park, Kyung Chan Yeom, Young Il Oh, Su Jin Park, Young Soo Kang, Min Ho Yoo, Hyang-Sook Jung, Yuri Jang, Ye Jin
AuthorAffiliation	1 Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea 2 Department of Functional Genomics, University of Science and Technology, Daejeon 305-350, Korea 3 Pfizer Global Research and Development, 10770 Science Center Drive, San Diego, California 92121, USA
AuthorAffiliation_xml	– name: 2 Department of Functional Genomics, University of Science and Technology, Daejeon 305-350, Korea – name: 3 Pfizer Global Research and Development, 10770 Science Center Drive, San Diego, California 92121, USA – name: 1 Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea
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SubjectTerms	Biochemistry Biomedical and Life Sciences Biomedicine Biotechnology Carcinoma, Hepatocellular - enzymology Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - metabolism Carcinoma, Hepatocellular - pathology Carrier Proteins - genetics Carrier Proteins - metabolism Cell Biology Cell Line, Tumor Cell Survival - physiology Gene Expression Gene Knockdown Techniques Glucose Transporter Type 3 - biosynthesis Glucose Transporter Type 3 - genetics Glycolysis Humans Lactic Acid - metabolism Life Sciences Liver Neoplasms - enzymology Liver Neoplasms - genetics Liver Neoplasms - metabolism Liver Neoplasms - pathology Membrane Proteins - deficiency Membrane Proteins - genetics Membrane Proteins - metabolism Research Article Thyroid Hormone-Binding Proteins Thyroid Hormones - deficiency Thyroid Hormones - genetics Thyroid Hormones - metabolism 생물학
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Title	Metabolic signature genes associated with susceptibility to pyruvate kinase, muscle type 2 gene ablation in cancer cells
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