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 language | English |
|---|---|
| Article number | 104 |
| Journal | Cell Death Discovery |
| Volume | 4 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Dec 1 2018 |
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All Science Journal Classification (ASJC) codes
- Immunology
- Cellular and Molecular Neuroscience
- Cell Biology
- Cancer Research
Cite this
Polyamine flux suppresses histone lysine demethylases and enhances ID1 expression in cancer stem cells. / Tamari, Keisuke; Konno, Masamitsu; Asai, Ayumu; Koseki, Jun; Hayashi, Kazuhiko; Kawamoto, Koichi; Murai, Noriyuki; Matsufuji, Senya; Isohashi, Fumiaki; Satoh, Taroh; Goto, Noriko; Tanaka, Shinji; Doki, Yuichiro; Mori, Masaki; Ogawa, Kazuhiko; Ishii, Hideshi.
In: Cell Death Discovery, Vol. 4, No. 1, 104, 01.12.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Polyamine flux suppresses histone lysine demethylases and enhances ID1 expression in cancer stem cells
AU - Tamari, Keisuke
AU - Konno, Masamitsu
AU - Asai, Ayumu
AU - Koseki, Jun
AU - Hayashi, Kazuhiko
AU - Kawamoto, Koichi
AU - Murai, Noriyuki
AU - Matsufuji, Senya
AU - Isohashi, Fumiaki
AU - Satoh, Taroh
AU - Goto, Noriko
AU - Tanaka, Shinji
AU - Doki, Yuichiro
AU - Mori, Masaki
AU - Ogawa, Kazuhiko
AU - Ishii, Hideshi
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85070980489&partnerID=8YFLogxK
U2 - 10.1038/s41420-018-0117-7
DO - 10.1038/s41420-018-0117-7
M3 - Article
AN - SCOPUS:85070980489
VL - 4
JO - Cell Death Discovery
JF - Cell Death Discovery
SN - 2058-7716
IS - 1
M1 - 104
ER -