We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Dclk1 distinguishes between tumor and normal stem cells in the intestine.
- Authors
Nakanishi, Yuki; Seno, Hiroshi; Fukuoka, Ayumi; Ueo, Taro; Yamaga, Yuichi; Maruno, Takahisa; Nakanishi, Naoko; Kanda, Keitaro; Komekado, Hideyuki; Kawada, Mayumi; Isomura, Akihiro; Kawada, Kenji; Sakai, Yoshiharu; Yanagita, Motoko; Kageyama, Ryoichiro; Kawaguchi, Yoshiya; Taketo, Makoto M; Yonehara, Shin; Chiba, Tsutomu
- 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); 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 gut, but recent reports have implicated it as a marker of differentiated cells (for example, Tuft cells). 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.
- Subjects
CANCER stem cells; BIOMARKERS; COLON cancer treatment; TARGETED drug delivery; REGRESSION analysis; POLYPS; KINASES; INTESTINAL tumors
- Publication
Nature Genetics, 2013, Vol 45, Issue 1, p98
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.2481