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KMID : 0578320130350040335
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Molecules and Cells
2013 Volume.35 No. 4 p.335 ~ p.341
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Metabolic Signature Genes Associated with Susceptibility to Pyruvate Kinase, Muscle Type 2 Gene Ablation in Cancer Cells
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Jung Yu-Ri
Jang Ye-Jin
Kang Min-Ho
Park Young-Soo
Oh Su-Jin
Lee Dong-Chul
Zhi Xie
Yoo Hyang-Sook
Park Kyung-Chan
Yeom Young-Il
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Abstract
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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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KEYWORD
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glycolysis, glycolysis-dependent, lactate, PKM2, SLC16A3
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