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.Epithelial-to-mesenchymal transition in tumour cells occurs through distinct intermediate states, associated with different metastatic potential, cellular properties, gene expression, and chromatin landscape

中文翻译：

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识别 EMT 期间发生的肿瘤过渡状态

在癌症中，上皮间质转化 (EMT) 与肿瘤干性、转移和对治疗的抵抗力有关。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。然而，这个想法没有直接的体内证据。在这里，我们筛选了皮肤和乳腺原发性肿瘤中的一大组细胞表面标志物，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，经过中间混合状态。尽管所有 EMT 亚群都表现出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表现出差异。他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，这些肿瘤亚群位于不同的生态位中，差异调节 EMT 过渡状态。肿瘤细胞中的上皮-间质转化通过不同的中间状态发生，与不同的转移潜力、细胞特性、基因表达和染色质景观相关