Polyamine flux suppresses histone lysine demethylases and enhances ID1 expression in cancer stem cells

Keisuke Tamari, Masamitsu Konno, Ayumu Asai, Jun Koseki, Kazuhiko Hayashi, Koichi Kawamoto, Noriyuki Murai, Senya Matsufuji, Fumiaki Isohashi, Taroh Satoh, Noriko Goto, Shinji Tanaka, Yuichiro Doki, Masaki Mori, Kazuhiko Ogawa, Hideshi Ishii

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Cancer stem cells (CSCs) exhibit tumorigenic potential and can generate resistance to chemotherapy and radiotherapy. A labeled ornithine decarboxylase (ODC, a rate-limiting enzyme involved in polyamine [PA] biosynthesis) degradation motif (degron) system allows visualization of a fraction of CSC-like cells in heterogeneous tumor populations. A labeled ODC degradation motif system allowed visualization of a fraction of CSC-like cells in heterogeneous tumor populations. Using this system, analysis of polyamine flux indicated that polyamine metabolism is active in CSCs. The results showed that intracellular polyamines inhibited the activity of histone lysine 4 demethylase enzymes, including lysine-specific demethylase-1 (LSD1). Chromatin immunoprecipitation with Pol II antibody followed by massively parallel DNA sequencing, revealed the global enrichment of Pol II in transcription start sites in CSCs. Increase of polyamines within cells resulted in an enhancement of ID1 gene expression. The results of this study reveal details of metabolic pathways that drive epigenetic control of cancer cell stemness and determine effective therapeutic targets in CSCs.

Original languageEnglish
Article number104
JournalCell Death Discovery
Volume4
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

All Science Journal Classification (ASJC) codes

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

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