Transcriptomic study of dormant gastrointestinal cancer stem cells.
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.
Department of Frontier Science for Cancer and Chemotherapy, Osaka                     University, Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Shimpei
S
Nishikawa
Dyah Laksmi
DL
Dewi
Hideshi
H
Ishii
Masamitsu
M
Konno
Naotsugu
N
Haraguchi
Yoshihiro
Y
Kano
Takahito
T
Fukusumi
Katsuya
K
Ohta
Yuko
Y
Noguchi
Miyuki
M
Ozaki
Daisuke
D
Sakai
Taroh
T
Satoh
Yuichiro
Y
Doki
Masaki
M
Mori
D018826:CD13 Antigens / Q000096:biosynthesis; D045744:Cell Line, Tumor; D004249:DNA Damage; D004260:DNA Repair; D019008:Drug Resistance, Neoplasm; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D000860:Hypoxia; D035683:MicroRNAs / Q000096:biosynthesis; D014411:Neoplastic Stem Cells / Q000473:pathology* / Q000502:physiology*; D018384:Oxidative Stress; D018800:Thy-1 Antigens / Q000096:biosynthesis; D059467:Transcriptome
D035683:MicroRNAs; C538984:Mirn182 microRNA, human; D018800:Thy-1 Antigens; D018826:CD13 Antigens