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

• 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
• ISSN: 1016-8478; 0219-1032
• DOI: 10.1007/s10059-013-2319-4

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).