Transcriptomic study of dormant gastrointestinal cancer stem cells.

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.

journal_name

Int J Oncol

authors

Nishikawa S,Dewi DL,Ishii H,Konno M,Haraguchi N,Kano Y,Fukusumi T,Ohta K,Noguchi Y,Ozaki M,Sakai D,Satoh T,Doki Y,Mori M

doi

10.3892/ijo.2012.1531

subject

Has Abstract

pub_date

2012-09-01 00:00:00

pages

979-84

issue

3

eissn

1019-6439

issn

1791-2423

journal_volume

41

pub_type

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