title: Lysine Demethylase LSD1 Coordinates Glycolytic and Mitochondrial Metabolism in Hepatocellular Carcinoma Cells.
abstract: The hallmark of most cancer cells is the metabolic shift from mitochondrial to glycolytic metabolism for adapting to the surrounding environment. Although epigenetic modification is intimately linked to cancer, the molecular mechanism, by which epigenetic factors regulate cancer metabolism, is poorly understood. Here, we show that lysine-specific demethylase-1 (LSD1, KDM1A) has an essential role in maintaining the metabolic shift in human hepatocellular carcinoma cells. Inhibition of LSD1 reduced glucose uptake and glycolytic activity, with a concurrent activation of mitochondrial respiration. These metabolic changes coexisted with the inactivation of the hypoxia-inducible factor HIF1α, resulting in a decreased expression of GLUT1 and glycolytic enzymes. In contrast, during LSD1 inhibition, a set of mitochondrial metabolism genes was activated with the concomitant increase of methylated histone H3 at lysine 4 in the promoter regions. Consistently, both LSD1 and GLUT1 were significantly overexpressed in carcinoma tissues. These findings demonstrate the epigenetic plasticity of cancer cell metabolism, which involves an LSD1-mediated mechanism.
authors: Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan Department of Neurosurgery, Faculty of Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors: Akihisa
authors: A
authors: Sakamoto
authors: Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan mnakao@gpo.kumamoto-u.ac.jp s-hino@kumamoto-u.ac.jp.
authors: Shinjiro
authors: S
authors: Hino
authors: Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
authors: Katsuya
authors: K
authors: Nagaoka
authors: Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
authors: Kotaro
authors: K
authors: Anan
authors: Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
authors: Ryuta
authors: R
authors: Takase
authors: Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
authors: Haruka
authors: H
authors: Matsumori
authors: Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo, Japan.
authors: Hidenori
authors: H
authors: Ojima
authors: Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo, Japan.
authors: Yae
authors: Y
authors: Kanai
authors: Department of Neurosurgery, Faculty of Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors: Kazunori
authors: K
authors: Arita
authors: Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Tokyo, Japan. mnakao@gpo.kumamoto-u.ac.jp s-hino@kumamoto-u.ac.jp.
authors: Mitsuyoshi
authors: M
authors: Nakao
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000473:pathology; D015870:Gene Expression; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D006019:Glycolysis; D056945:Hep G2 Cells; D056466:Histone Demethylases / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology; D008113:Liver Neoplasms / Q000201:enzymology* / Q000473:pathology; D008745:Methylation; D016513:Mice, SCID; D008930:Mitochondria, Liver / Q000201:enzymology*; D009368:Neoplasm Transplantation; D011499:Protein Processing, Post-Translational; D047368:Tumor Burden
chemical_list: D051272:Glucose Transporter Type 1; C497442:HIF1A protein, human; D006657:Histones; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C495677:SLC2A1 protein, human; D056466:Histone Demethylases; C495195:KDM1A protein, human