Dclk1 distinguishes between tumor and normal stem cells in the intestine

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


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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
Author's alias:	妹尾, 浩
Keywords:	tumor initiating cell cancer stem cell lineage tracing colon cancer Dcamkl1
Issue Date:	2-Dec-2012
Publisher:	Nature Publishing Group
Journal title:	Nature Genetics
DOI:	10.1038/ng.2481
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)1–4; 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.
Description:	癌幹細胞を特定するマーカー同定に成功 : 新世代の癌治療法開発に期待.京都大学プレスリリース.2012-12-03.
Rights:	© 2012 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. 許諾条件により本文は2013-06-02に公開.
URI:	http://hdl.handle.net/2433/163077
Related Link:	http://www.kyoto-u.ac.jp/ja/news_data/h/h1/news6/2012/121203_1.htm
Appears in Collections:	Journal Articles

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