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首页> 外文期刊>Nature cell biology >Adult interfollicular tumour-initiating cells are reprogrammed into an embryonic hair follicle progenitor-like fate during basal cell carcinoma initiation
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Adult interfollicular tumour-initiating cells are reprogrammed into an embryonic hair follicle progenitor-like fate during basal cell carcinoma initiation

机译：在基础细胞癌发作期间，将成年的小泡间肿瘤引发细胞重编程为胚胎毛囊祖细胞样的命运

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Basal cell carcinoma, the most frequent human skin cancer, arises from activating hedgehog (HH) pathway mutations; however, little is known about the temporal changes that occur in tumour-initiating cells from the first oncogenic hit to the development of invasive cancer. Using an inducible mouse model enabling the expression of a constitutively active Smoothened mutant (SmoM2) in the adult epidermis, we carried out transcriptional profiling of SmoM2-expressing cells at different times during cancer initiation. We found that tumour-initiating cells are massively reprogrammed into a fate resembling that of embryonic hair follicle progenitors (EHFPs). Wnt/ β-catenin signalling was very rapidly activated following SmoM2 expression in adult epidermis and coincided with the expression of EHFP markers. Deletion of β-catenin in adult SmoM2-expressing cells prevents EHFP reprogramming and tumour initiation. Finally, human basal cell carcinomas also express genes of the Wnt signalling and EHFP signatures.
机译：基底细胞癌是人类最常见的皮肤癌，源于激活刺猬（HH）途径的突变。然而，从最初的致癌基因发生到侵袭性癌症发展，肿瘤引发细胞发生的时间变化知之甚少。使用诱导型小鼠平滑肌突变体（SmoM2）在成人表皮中表达的诱导型小鼠模型，我们在癌症发作期间的不同时间进行了SmoM2表达细胞的转录分析。我们发现，肿瘤引发细胞被大量重编程为类似于胚胎毛囊祖细胞（EHFP）的命运。在成年表皮中SmoM2表达后，Wnt /β-catenin信号被非常迅速地激活，并与EHFP标记的表达相吻合。成人SmoM2表达细胞中β-catenin的缺失可阻止EHFP重新编程和肿瘤的发生。最后，人类基底细胞癌还表达Wnt信号和EHFP签名的基因。

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