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上皮-间质转化的机制新见解及其对癌症的影响。

New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer.

机构信息

Whitehead Institute for Biomedical Research, Cambridge, MA, USA.

MIT Ludwig Center for Molecular Oncology, Cambridge, MA, USA.

出版信息

Nat Rev Mol Cell Biol. 2019 Feb;20(2):69-84. doi: 10.1038/s41580-018-0080-4.

Abstract

Epithelial-mesenchymal transition (EMT) is a cellular programme that is known to be crucial for embryogenesis, wound healing and malignant progression. During EMT, cell-cell and cell-extracellular matrix interactions are remodelled, which leads to the detachment of epithelial cells from each other and the underlying basement membrane, and a new transcriptional programme is activated to promote the mesenchymal fate. In the context of neoplasias, EMT confers on cancer cells increased tumour-initiating and metastatic potential and a greater resistance to elimination by several therapeutic regimens. In this Review, we discuss recent findings on the mechanisms and roles of EMT in normal and neoplastic tissues, and the cell-intrinsic signals that sustain expression of this programme. We also highlight how EMT gives rise to a variety of intermediate cell states between the epithelial and the mesenchymal state, which could function as cancer stem cells. In addition, we describe the contributions of the tumour microenvironment in inducing EMT and the effects of EMT on the immunobiology of carcinomas.

摘要

上皮-间充质转化(EMT)是一个众所周知的细胞程序,对于胚胎发生、伤口愈合和恶性进展至关重要。在 EMT 过程中,细胞-细胞和细胞-细胞外基质的相互作用被重塑,导致上皮细胞彼此分离和基底膜的分离,并激活新的转录程序以促进间充质命运。在肿瘤学中,EMT 赋予癌细胞更高的肿瘤起始和转移潜力,并对多种治疗方案的消除具有更大的抵抗力。在这篇综述中,我们讨论了 EMT 在正常和肿瘤组织中的机制和作用,以及维持该程序表达的细胞内信号的最新发现。我们还强调了 EMT 如何产生上皮和间充质状态之间的多种中间细胞状态,这些状态可能作为癌症干细胞发挥作用。此外,我们描述了肿瘤微环境在诱导 EMT 中的作用以及 EMT 对癌免疫生物学的影响。

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