title: Histone demethylase LSD1 controls the phenotypic plasticity of cancer cells.
abstract: Epigenetic mechanisms underlie the phenotypic plasticity of cells, while aberrant epigenetic regulation through genetic mutations and/or misregulated expression of epigenetic factors leads to aberrant cell fate determination, which provides a foundation for oncogenic transformation. Lysine-specific demethylase-1 (LSD1, KDM1A) removes methyl groups from methylated proteins, including histone H3, and is frequently overexpressed in various types of solid tumors and hematopoietic neoplasms. While LSD1 is involved in a wide variety of normal physiological processes, including stem cell maintenance and differentiation, it is also a key player in oncogenic processes, including compromised differentiation, enhanced cell motility and metabolic reprogramming. Here, we present an overview of how LSD1 epigenetically regulates cellular plasticity through distinct molecular mechanisms in different biological contexts. Targeted inhibition of the context-dependent activities of LSD1 may provide a highly selective means to eliminate cancer cells.
authors.affiliation: Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan. s-hino@kumamoto-u.ac.jp.
authors.forename: Shinjiro
authors.initials: S
authors.lastname: Hino
authors.affiliation: Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
authors.forename: Kensaku
authors.initials: K
authors.lastname: Kohrogi
authors.affiliation: Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan. mnakao@gpo.kumamoto-u.ac.jp.|Core Research for Evolutional Science and Technology (CREST), Japan Agency for Medical Research and Development, Tokyo, Japan. mnakao@gpo.kumamoto-u.ac.jp.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Nakao
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism; D044127:Epigenesis, Genetic; D015973:Gene Expression Regulation, Leukemic; D056466:Histone Demethylases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008745:Methylation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype
chemical_list: D006657:Histones; D056466:Histone Demethylases; C495195:KDM1A protein, human
keywords: Cancer metabolism; chromatin; histone demethylation; lysine-specific demethylase-1; stemness