Defining the clonal dynamics leading to mouse skin tumour initiation.
Defining the clonal dynamics leading to mouse skin tumour initiation.
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DOI：
10.1038/nature19069
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发表时间：
2016-08-18
期刊：
影响因子：
64.8
通讯作者：
Blanpain, Cedric
中科院分区：
文献类型：
--
作者：
Sanchez-Danes, Adriana;Hannezo, Edouard;Larsimont, Jean-Christophe;Liagre, Melanie;Youssef, Khalil Kass;Simons, Benjamin D.;Blanpain, Cedric
致癌突变后细胞动力学发生的变化导致肿瘤的发展目前尚不清楚。在这里，使用皮肤表皮作为模型，我们评估了致癌hedgehog信号在不同细胞群中的影响及其诱导基底细胞癌（人类最常见的癌症）的能力。我们发现，只有干细胞，而不是祖细胞，有能力启动肿瘤形成后致癌刺猬信号。有趣的是，这种差异是由于肿瘤生长在癌基因靶向干细胞的分层组织，其特征是增加对称的自我更新分裂和更高的p53依赖性抗凋亡，导致快速克隆扩增和进展为浸润性肿瘤。我们的工作揭示了癌基因靶向细胞诱导肿瘤形成的能力不仅取决于它们的长期存活和扩增，而且还取决于起源癌细胞的特定克隆动力学。
The changes that occur in cell dynamics following oncogenic mutation that lead to the development of tumours are currently unknown. Here, using skin epidermis as a model, we assessed the impact 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, were competent to initiate tumour formation upon oncogenic hedgehog signalling. Interestingly, this difference was due to the hierarchical organization of tumour growth in oncogene-targeted stem cells, characterized by an increase of 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 not only dependent on their long-term survival and expansion, but also on the specific clonal dynamics of the cancer cell of origin.
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影响因子：
20.3
作者：
Uhmann, Anja;Dittmann, Kai;Hahn, Heidi
通讯作者：
Hahn, Heidi
DOI：
10.1073/pnas.1013098108
发表时间：
2011-03-08
影响因子：
11.1
作者：
Wong, Sunny Y.;Reiter, Jeremy F.
通讯作者：
Reiter, Jeremy F.
影响因子：
21.3
作者：
Youssef, Khalil Kass;Lapouge, Gaelle;Blanpain, Cedric
通讯作者：
Blanpain, Cedric
影响因子：
50.3
作者：
Schueller, Ulrich;Heine, Vivi M.;Mao, Junhao;Kho, Alvin T.;Dillon, Allison K.;Han, Young-Goo;Huillard, Emmanuelle;Sun, Tao;Ligon, Azra H.;Qian, Ying;Ma, Qiufu;Alvarez-Buylla, Arturo;McMahon, Andrew P.;Rowitch, David H.;Ligon, Keith L.
通讯作者：
Ligon, Keith L.
DOI：
10.1126/science.1242281
发表时间：
2014-06-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Blanpain C;Fuchs E
通讯作者：
Fuchs E