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摘要 : 本文对从初始癌化刺激到侵袭性肿瘤发展的肿瘤发生过程进行了量化分析。

 本文对从初始癌化刺激到侵袭性肿瘤发展的肿瘤发生过程进行了量化分析。Cédric Blanpain及同事在不同的表皮细胞中引入了同一种致癌变异——致癌刺猬信号,并衡量了它们诱发基底细胞癌的能力。只有皮肤干细胞能形成肿瘤,而其后代不能。这是因为致癌基因针对的干细胞能够增加自我更新对称分裂,且p53依赖的细胞凋亡抵抗作用更强。


Defining the clonal dynamics leading to mouse skin tumour initiation


The changes in cell dynamics after oncogenic mutation that lead to the development of tumours are currently unknown. Here, using skin epidermis as a model, we assessed the effect of oncogenic hedgehog signalling in distinct cell populations and their capacity to induce basal cell carcinoma, the most frequent cancer in humans. We found that only stem cells, and not progenitors, initiated tumour formation upon oncogenic hedgehog signalling. This difference was due to the hierarchical organization of tumour growth in oncogene-targeted stem cells, characterized by an increase in symmetric self-renewing divisions and a higher p53-dependent resistance to apoptosis, leading to rapid clonal expansion and progression into invasive tumours. Our work reveals that the capacity of oncogene-targeted cells to induce tumour formation is dependent not only on their long-term survival and expansion, but also on the specific clonal dynamics of the cancer cell of origin.

来源: Nature 浏览次数:1


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