Nakanishi, Y. et al. (2013) Dclk1 distinguishes between tumor and normal stem cells in the intestine. Nature Genetics, 45, pp. 98-103. (doi: 10.1038/ng.2481) (PMID:23202126)
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Abstract
There is great interest in tumor stem cells (TSCs) as potential therapeutic targets; however, cancer therapies targeting TSCs are limited. A drawback is that TSC markers are often shared by normal stem cells (NSCs)1,2,3,4; thus, therapies that target these markers may cause severe injury to normal tissues. To identify a potential TSC-specific marker, we focused on doublecortin-like kinase 1 (Dclk1). Dclk1 was reported as a candidate NSC marker in the gut5,6, but recent reports have implicated it as a marker of differentiated cells (for example, Tuft cells)7,8. Using lineage-tracing experiments, we show here that Dclk1 does not mark NSCs in the intestine but instead marks TSCs that continuously produce tumor progeny in the polyps of ApcMin/+ mice. Specific ablation of Dclk1-positive TSCs resulted in a marked regression of polyps without apparent damage to the normal intestine. Our data suggest the potential for developing a therapy for colorectal cancer based on targeting Dclk1-positive TSCs.
Item Type: | Articles (Letter) |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Suzuki, Dr Ayumi |
Authors: | Nakanishi, Y., Seno, H., Fukuoka, A., Ueo, T., Yamaga, Y., Maruno, T., Nakanishi, N., Kanda, K., Komekado, H., Kawada, M., Isomura, A., Kawada, K., Sakai, Y., Yanagita, M., Kageyama, R., Kawaguchi, Y., Taketo, M. M., Yonehara, S., and Chiba, T. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | Nature Genetics |
Publisher: | Nature Research |
ISSN: | 1061-4036 |
ISSN (Online): | 1546-1718 |
Published Online: | 02 December 2012 |
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