title: Metabolic signature genes associated with susceptibility to pyruvate kinase, muscle type 2 gene ablation in cancer cells.
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).
authors.affiliation: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Jung
authors.forename: Ye Jin
authors.initials: YJ
authors.lastname: Jang
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Kang
authors.forename: Young Soo
authors.initials: YS
authors.lastname: Park
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Oh
authors.forename: Dong Chul
authors.initials: DC
authors.lastname: Lee
authors.forename: Zhi
authors.initials: Z
authors.lastname: Xie
authors.forename: Hyang-Sook
authors.initials: HS
authors.lastname: Yoo
authors.forename: Kyung Chan
authors.initials: KC
authors.lastname: Park
authors.forename: Young Il
authors.initials: YI
authors.lastname: Yeom
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D051274:Glucose Transporter Type 3 / Q000096:biosynthesis / Q000235:genetics; D006019:Glycolysis; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D013963:Thyroid Hormones / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D002352:Carrier Proteins; D051274:Glucose Transporter Type 3; D019344:Lactic Acid; D008565:Membrane Proteins; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins; C495687:SLC2A3 protein, human