Transcriptomic study of dormant gastrointestinal cancer stem cells

Shimpei Nishikawa, Dyah Laksmi Dewi, Hideshi Ishii, Masamitsu Konno, Naotsugu Haraguchi, Yoshihiro Kano, Takahito Fukusumi, Katsuya Ohta, Yuko Noguchi, Miyuki Ozaki, Daisuke Sakai, Taroh Satoh, Yuichiro Doki, Masaki Mori

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

We previously discovered the coexistence of dormant and proliferating cancer stem cells (CSCs) in gastrointestinal cancer, which leads to chemoradiation resistance. CD13-/CD90+ proliferating liver CSCs are sensitive to chemotherapy, and CD13+/CD90- dormant CSCs have a limited proliferation ability, survive in hypoxic areas with reduced oxidative stress, and relapse and metastasize to other organs. In such CD13+ dormant cells, non-homologous end-joining, an error-prone repair mechanism, is dominant after DNA damage, whereas high-fidelity homologous recombination is apparent in CD13- proliferating cells, suggesting the significance of dormancy as an essential protective mechanism of therapy resistance. However, this mechanism may also play a role in the generation and accumulation of heterogeneity during cancer progression, although the exact mechanism remains to be understood. Through transcriptomic study, we elucidated the underlying epigenetic mechanism for malignant behavior of dormant CSCs, i.e., simultaneous activation of several pathways including EZH2- and TP53-related proteins in response to microRNA101, suggesting that a pharmacogenomic approach would open an era to novel molecular targeting cancer therapy.

Original languageEnglish
Pages (from-to)979-984
Number of pages6
JournalInternational journal of oncology
Volume41
Issue number3
DOIs
Publication statusPublished - Sep 1 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Nishikawa, S., Dewi, D. L., Ishii, H., Konno, M., Haraguchi, N., Kano, Y., Fukusumi, T., Ohta, K., Noguchi, Y., Ozaki, M., Sakai, D., Satoh, T., Doki, Y., & Mori, M. (2012). Transcriptomic study of dormant gastrointestinal cancer stem cells. International journal of oncology, 41(3), 979-984. https://doi.org/10.3892/ijo.2012.1531