Dclk1 distinguishes between tumor and normal stem cells in the intestine

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)

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)
• 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