Identification of the tumour transition states occurring during EMT
Identification of the tumour transition states occurring during EMT
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DOI：
10.1038/s41586-018-0040-3
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发表时间：
2018-04-26
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：
Pastushenko, Ievgenia;Brisebarre, Audrey;Blanpain, Cedric
在癌症中，上皮到间质转化（EMT）与肿瘤的干性、转移和对治疗的抵抗有关。最近有人提出，EMT不是一个二元过程，而是通过不同的中间状态发生的。然而，这一观点并没有直接的活体证据。在这里，我们筛选了皮肤和乳腺原发性肿瘤中的大量细胞表面标记物，并确定了与不同EMT阶段相关的多个肿瘤亚群的存在：从上皮到完全间充质状态，经过中间杂交状态。尽管所有EMT亚群具有相似的肿瘤增殖细胞能力，但它们在细胞可塑性、侵袭性和转移潜力方面存在差异。它们的转录和表观遗传景观确定了控制这些不同EMT过渡状态的潜在基因调控网络、转录因子和信号通路。最后，这些肿瘤亚群定位于不同的生态位，不同的生态位调节EMT过渡状态。
In cancer, the epithelial-to-mesenchymal transition (EMT) is associated with tumour stemness, metastasis and resistance to therapy. It has recently been proposed that, rather than being a binary process, EMT occurs through distinct intermediate states. However, there is no direct in vivo evidence for this idea. Here we screen a large panel of cell surface markers in skin and mammary primary tumours, and identify the existence of multiple tumour subpopulations associated with different EMT stages: from epithelial to completely mesenchymal states, passing through intermediate hybrid states. Although all EMT subpopulations presented similar tumour-propagating cell capacity, they displayed differences in cellular plasticity, invasiveness and metastatic potential. Their transcriptional and epigenetic landscapes identify the underlying gene regulatory networks, transcription factors and signalling pathways that control these different EMT transition states. Finally, these tumour subpopulations are localized in different niches that differentially regulate EMT transition states.