Dclk1 distinguishes between tumor and normal stem cells in the intestine
Dclk1 distinguishes between tumor and normal stem cells in the intestine
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DOI：
10.1038/ng.2481
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发表时间：
2013-01-01
期刊：
影响因子：
30.8
通讯作者：
Chiba, Tsutomu
中科院分区：
文献类型：
--
作者：
Nakanishi, Yuki;Seno, Hiroshi;Chiba, Tsutomu
肿瘤干细胞(TSCs)作为潜在的治疗靶点引起了人们的极大兴趣，但针对TSCs的癌症治疗是有限的。缺点是TSC标记物通常被正常干细胞(NSCs)共享(1-4)；因此，针对这些标记物的治疗可能会对正常组织造成严重损伤。为了确定一个潜在的TSC特异性标记，我们将重点放在双皮质醇样激酶1(Dclk1)上。Dclk1被报道为肠道神经干细胞的候选标记(5，6)，但最近的报道表明它是分化细胞(如簇状细胞)的标记(7，8)。利用谱系追踪实验，我们在这里表明，Dclk1不标记肠道中的NSCs，而是标记在APC(Min/+)小鼠的息肉中持续产生肿瘤后代的TSCs。Dclk1阳性TSCs的特异性消融可使息肉显著消退，而对正常肠道无明显损害。我们的数据表明，基于靶向Dclk1阳性的TSC，开发一种治疗结直肠癌的方法是有潜力的。
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 gut(5,6), 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 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.