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

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.

Journal

• Nature Genetics

  Nature Genetics 45 (1), 98-103, 2012-12-02

  Nature Publishing Group

Keywords

• tumor initiating cell
• cancer stem cell
• lineage tracing
• colon cancer
• Dcamkl1

Details

• CRID: 1050845760675218560
• NII Article ID: 120004996279
• NII Book ID: AA1084279X
• ISSN: 10614036
• ISSN: 15461718
• ISSN: http://id.crossref.org/issn/10614036
• DOI: 10.1038/ng.2481
• HANDLE: 2433/163077
• Web Site: http://www.nature.com/articles/ng.2481.pdf
• Web Site: http://www.nature.com/articles/ng.2481
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN