title: Dclk1 distinguishes between tumor and normal stem cells in the intestine.
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 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.
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nakanishi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Seno
authors.forename: Ayumi
authors.initials: A
authors.lastname: Fukuoka
authors.forename: Taro
authors.initials: T
authors.lastname: Ueo
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yamaga
authors.forename: Takahisa
authors.initials: T
authors.lastname: Maruno
authors.forename: Naoko
authors.initials: N
authors.lastname: Nakanishi
authors.forename: Keitaro
authors.initials: K
authors.lastname: Kanda
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Komekado
authors.forename: Mayumi
authors.initials: M
authors.lastname: Kawada
authors.forename: Akihiro
authors.initials: A
authors.lastname: Isomura
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawada
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Sakai
authors.forename: Motoko
authors.initials: M
authors.lastname: Yanagita
authors.forename: Ryoichiro
authors.initials: R
authors.lastname: Kageyama
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: Makoto M
authors.initials: MM
authors.lastname: Taketo
authors.forename: Shin
authors.initials: S
authors.lastname: Yonehara
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
mesh_terms: D000818:Animals; D000089742:Doublecortin-Like Kinases; D005260:Female; D023061:Gene Order; D007413:Intestinal Mucosa / Q000378:metabolism*; D007414:Intestinal Neoplasms / Q000235:genetics* / Q000473:pathology; D007417:Intestinal Polyps / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007422:Intestines / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C117347:DCLK1 protein, human; D000089742:Doublecortin-Like Kinases; D017346:Protein Serine-Threonine Kinases