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Histone demethylase LSD1 controls the phenotypic plasticity of cancer cells.

Authors
  • Hino, Shinjiro1
  • Kohrogi, Kensaku2
  • Nakao, Mitsuyoshi3, 4
  • 1 Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan. [email protected] , (Japan)
  • 2 Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan. , (Japan)
  • 3 Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan. [email protected] , (Japan)
  • 4 Core Research for Evolutional Science and Technology (CREST), Japan Agency for Medical Research and Development, Tokyo, Japan. [email protected] , (Japan)
Type
Published Article
Journal
Cancer science
Publication Date
Sep 01, 2016
Volume
107
Issue
9
Pages
1187–1192
Identifiers
DOI: 10.1111/cas.13004
PMID: 27375009
Source
Medline
Keywords
Language
English
License
Unknown

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. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

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