Cell-Type-Specific Chromatin States Differentially Prime Squamous Cell Carcinoma Tumor-Initiating Cells for Epithelial to Mesenchymal Transition.
Cell-Type-Specific Chromatin States Differentially Prime Squamous Cell Carcinoma Tumor-Initiating Cells for Epithelial to Mesenchymal Transition.
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DOI：
10.1016/j.stem.2016.10.018
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发表时间：
2017-02-02
期刊：
影响因子：
23.9
通讯作者：
Blanpain C
中科院分区：
文献类型：
--
作者：
Latil M;Nassar D;Beck B;Boumahdi S;Wang L;Brisebarre A;Dubois C;Nkusi E;Lenglez S;Checinska A;Vercauteren Drubbel A;Devos M;Declercq W;Yi R;Blanpain C
癌细胞中的上皮间质转化（EMT）与转移、严重性和治疗耐药性相关。有些肿瘤会经历 EMT，而另一些则不会，这可能反映了其起源细胞的内在特性。然而，这种可能性很大程度上尚未被探索。通过将相同的致癌突变靶向离散的皮肤区室，我们发现细胞类型特异性染色质和转录状态对肿瘤发生 EMT 的作用存在差异。源自滤泡间表皮 (IFE) 的鳞状细胞癌 (SCC) 通常分化良好，而源自毛囊 (HF) 干细胞的 SCC 经常表现出 EMT，有效形成继发性肿瘤，并具有增加的转移潜力。转录和表观基因组分析表明，IFE 和 HF 肿瘤起始细胞具有独特的染色质景观和与肿瘤发生和 EMT 相关的基因调控网络，这些网络与关键上皮和 EMT 转录因子结合位点的可及性相关。这些发现强调了染色质状态和转录启动在决定肿瘤表型和 EMT 中的重要性。简而言之，Latil 及其同事表明，肿瘤表型和 EMT 倾向是由细胞类型特异性染色质和起源癌细胞的转录状态决定的。这些发现提供了对染色质景观和基因调控网络引导肿瘤起始细胞进行 EMT 的机制的深入了解。
Epithelial to mesenchymal transition (EMT) in cancer cells has been associated with metastasis, sternness, and resistance to therapy. Some tumors undergo EMT while others do not, which may reflect intrinsic properties of their cell of origin. However, this possibility is largely unexplored. By targeting the same oncogenic mutations to discrete skin compartments, we show that cell-type-specific chromatin and transcriptional states differentially prime tumors to EMT. Squamous cell carcinomas (SCCs) derived from interfollicular epidermis (IFE) are generally well differentiated, while hair follicle (HF) stem cell-derived SCCs frequently exhibit EMT, efficiently form secondary tumors, and possess increased metastatic potential. Transcriptional and epigenomic profiling revealed that IFE and HF tumor-initiating cells possess distinct chromatin landscapes and gene regulatory networks associated with tumorigenesis and EMT that correlate with accessibility of key epithelial and EMT transcription factor binding sites. These findings highlight the importance of chromatin states and transcriptional priming in dictating tumor phenotypes and EMT. In Brief Latil and colleagues show that tumor phenotypes and propensity for EMT are dictated by cell-type-specific chomatin and transcriptional states of the cancer cell of origin. These findings provide insight into mechanisms through which chromatin landscapes and gene regulatory networks prime tumor-initiating cells to undergo EMT.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
64.8
作者：
Boumahdi, Soufiane;Driessens, Gregory;Blanpain, Cedric
通讯作者：
Blanpain, Cedric
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
影响因子：
64.5
作者：
Horsley, Valerie;Aliprantis, Antonios O.;Fuchs, Elaine
通讯作者：
Fuchs, Elaine