Wounding mobilizes hair follicle stem cells to form tumors
Wounding mobilizes hair follicle stem cells to form tumors
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DOI：
10.1073/pnas.1013098108
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发表时间：
2011-03-08
影响因子：
11.1
通讯作者：
Reiter, Jeremy F.
中科院分区：
文献类型：
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作者：
Wong, Sunny Y.;Reiter, Jeremy F.
各种各样的人类癌症都与伤害有关。尽管干细胞参与创伤后的组织再生，但这些细胞是否也对上皮性肿瘤起作用尚不清楚。人类基底细胞癌(BCC)与Hedgehog(HH)信号失活有关，通常是通过获得Smoothens(Smo)突变。我们已经发现，毛囊隆起和次级毛胚的干细胞表达一种激活形式的Smo不会诱导强大的HH信号或产生BCC。然而，创伤将这些细胞从滤泡重新招募到伤口部位，在那里下游的HH信号转导被去抑制，导致浅表的BCC样肿瘤。这些发现表明，基底细胞癌样瘤可以起源于滤泡干细胞，并为创伤和肿瘤发生之间的联系提供了解释。
A wide variety of human cancers are associated with injury. Although stem cells participate in tissue regeneration after wounding, it is unclear whether these cells also contribute to epithelial tumors. Human basal cell carcinomas (BCCs) are associated with misactivation of Hedgehog (Hh) signaling, commonly through acquisition of mutations in Smoothened (Smo). We have found that expression of an activated form of Smo by stem cells of the hair-follicle bulge and secondary hair germ does not induce robust Hh signaling or produce BCCs. However, wounding recruits these cells from the follicle to the wound site, where downstream Hh signal transduction is derepressed, giving rise to superficial BCC-like tumors. These findings demonstrate that BCC-like tumors can originate from follicular stem cells and provide an explanation for the association between wounding and tumorigenesis.