Distinct epigenetic regulation of tumor suppressor genes in putative cancer stem cells of solid tumors

Hiroyuki Yasuda, Kenzo Soejima, Hideo Watanabe, Ichiro Kawada, Ichiro Nakachi, Satoshi Yoda, Sohei Nakayama, Ryosuke Satomi, Shinnosuke Ikemura, Hideki Terai, Takashi Sato, Sadafumi Suzuki, Yumi Matsuzaki, Katsuhiko Naoki, Akitoshi Ishizaka

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Epigenetic gene regulation plays essential roles in differentiation of embryonic and tissue stem cells. In these benign undifferentiated cells, some polycomb targeted genes are kept in a state of DNA hypomethylation and they have a distinct chromatin signature termed bivalent chromatin structure to maintain their plasticity. We hypothesized that cancer stem cells (CSC), the malignant counterpart of these cells, are also under the control of epigenetics like benign stem cells. We compared the DNA methylation and chromatin structure in 10 tumor suppressor genes between CSC and differentiated cancer cells of MCF7 and Huh7 cells. We found that the level of DNA methylation was indeed significantly lower in CSC, while surprisingly, the bivalent chromatin structure was more ubiquitously seen in differentiated cancer cells compared to CSC. However, repressive marks of chromatin structure, namely H3K27me3 and EZH2, were significantly lower in CSC. As a consequence, CSC remained in a higher transcriptionally active chromatin state compared to differentiated cancer cells. We found that the differentiation of CSCs is also epigenetically regulated. These findings could help towards a comprehensive understanding of CSC, and also improve the development of eradicative therapies against human malignancies.

Original languageEnglish
Pages (from-to)1537-1546
Number of pages10
JournalInternational Journal of Oncology
Issue number6
StatePublished - Dec 2010
Externally publishedYes


  • Cancer stem cells
  • DNA methylation
  • Epigenetics


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