Journal
DIGESTIVE AND LIVER DISEASE
Volume 50, Issue 12, Pages 1353-1361Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.dld.2018.06.011
Keywords
Colorectal cancer; Microarray analysis; Tumor stem cells
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Funding
- KAKENHI [15J03212, 25112707, 26293173, 16K09394, 16K15427, 17H04157]
- Kobayashi Foundation for Cancer Research
- Naito Foundation
- Princess Takamatsu Cancer Research Fund [13-24514]
- Mitsubishi Foundation
- Mochida Foundation
- Japanese Society of Gastroenterology
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Background: Accumulating evidence has shown the existence of tumor stem cells with therapeutic potential. Previously, we reported that doublecortin like kinase I (Dclk1) marks tumor stem cells but not normal stem cells in the intestine of Apc(Min/+) mice, and that Dclk1- and Lgr5-double positive tumor cells are the tumor stem cells of intestinal tumors. Aim: To investigate molecules highly expressed in the Dclk1(+) normal intestinal and Dclk1(+) tumor cells in Apc(Min/+) mice. Methods: We used microarray analyses to examine the gene expression profile of Dclk1(+) cells in both mouse normal intestinal epithelium and Apc(Min/+) mouse intestinal tumors. We also performed immunofluorescence analyses. Results: Genes related to microtubules and the actin cytoskeleton (e.g., Rac2), and members of the Src family kinases (i.e., Hck, Lyn, Csk, and Ptpn6) were highly expressed in both Dclk1(+) normal intestinal and Dclk1(+) tumor cells. Phosphorylated Hck and phosphorylated Lyn were expressed in Lgr5(+) cells in the intestinal tumors of Lgr(5EGFP-IRES- CreERT2/+); Apc(Min/+) mice. Conclusion: We revealed factors that are highly expressed in Dclk1(+) intestinal tumor cells, which may help to develop cancer stem cell-targeted therapy in future. (C) 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
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