Basal cell carcinoma preferentially arises from stem cells within hair follicle and mechanosensory niches.
Basal cell carcinoma preferentially arises from stem cells within hair follicle and mechanosensory niches.
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DOI：
10.1016/j.stem.2015.02.006
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发表时间：
2015-04-02
期刊：
影响因子：
23.9
通讯作者：
Wong, Sunny Y.
中科院分区：
文献类型：
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作者：
Peterson, Shelby C.;Eberl, Markus;Vagnozzi, Alicia N.;Belkadi, Abdelmadjid;Veniaminova, Natalia A.;Verhaegen, Monique E.;Bichakjian, Christopher K.;Ward, Nicole L.;Dlugosz, Andrzej A.;Wong, Sunny Y.
基底细胞癌（BCC）的特征是PTCH 1的频繁丢失，导致Hedgehog通路的组成性激活。虽然基底细胞癌中Hedgehog的需要已经得到了很好的证实，但疾病起始细胞的身份及其所在的隔室仍然存在争议。通过使用几种可诱导的Cre驱动程序删除小鼠不同细胞区室中的Ptch1，我们在这里表明，多个毛囊干细胞群容易发展为BCC样肿瘤。相反，毛囊间表皮内的干细胞不能有效地形成肿瘤。值得注意的是，我们观察到，神经支配的Gli1表达祖细胞内mechanosensory触摸圆顶上皮是高度致瘤性。感觉神经激活正常触摸圆顶中的Hedgehog信号传导，而去神经支配减弱触摸圆顶衍生的肿瘤。总之，我们的研究确定了皮肤中不同干细胞群体之间不同的肿瘤易感性，突出了触摸圆顶上皮作为肿瘤形成的“热点”，并暗示皮肤神经作为肿瘤发生的介质。
Basal cell carcinoma (BCC) is characterized by frequent loss of PTCH1, leading to constitutive activation of the Hedgehog pathway. Although the requirement for Hedgehog in BCC is well-established, the identity of disease-initiating cells and the compartments in which they reside remain controversial. By using several inducible Cre drivers to delete Ptch1 in different cell compartments in mice, we show here that multiple hair follicle stem cell populations readily develop BCC-like tumors. In contrast, stem cells within the interfollicular epidermis do not efficiently form tumors. Notably, we observed that innervated Gli1-expressing progenitors within mechanosensory touch dome epithelia are highly tumorigenic. Sensory nerves activate Hedgehog signaling in normal touch domes, while denervation attenuates touch dome-derived tumors. Together, our studies identify varying tumor susceptibilities among different stem cell populations in the skin, highlight touch dome epithelia as “hot spots” for tumor formation, and implicate cutaneous nerves as mediators of tumorigenesis.
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影响因子：
23.9
作者：
Brownell, Isaac;Guevara, Elizabeth;Bai, C. Brian;Loomis, Cynthia A.;Joyner, Alexandra L.
通讯作者：
Joyner, Alexandra L.
影响因子：
6.5
作者：
Adolphe, Christelle;Nieuwenhuis, Erica;Wainwright, Brandon J.
通讯作者：
Wainwright, Brandon J.
DOI：
10.1038/nrc2503
发表时间：
2008-10
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
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影响因子：
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作者：
ENGLISH, KB;KAVKAVANNORMAN, D;HORCH, K
通讯作者：
HORCH, K
DOI：
10.1139/o95-070
发表时间：
1995-09-01
期刊：
BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE
影响因子：
--
作者：
Fradette, J;Godbout, MJ;Germain, L
通讯作者：
Germain, L