Dclk1 distinguishes between tumor and normal stem cells in the intestine.

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 Apc(Min/+) 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.

Citation

Yuki Nakanishi, Hiroshi Seno, Ayumi Fukuoka, Taro Ueo, Yuichi Yamaga, Takahisa Maruno, Naoko Nakanishi, Keitaro Kanda, Hideyuki Komekado, Mayumi Kawada, Akihiro Isomura, Kenji Kawada, Yoshiharu Sakai, Motoko Yanagita, Ryoichiro Kageyama, Yoshiya Kawaguchi, Makoto M Taketo, Shin Yonehara, Tsutomu Chiba. Dclk1 distinguishes between tumor and normal stem cells in the intestine. Nature genetics. 2013 Jan;45(1):98-103

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PMID: 23202126

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