上皮间质转化或转化 (EMT) 是一种细胞形状改变过程，在整个胚胎发生过程中反复使用，对于实现精确的身体规划至关重要。在成人中，在正常和病理条件下都可以观察到 EMT，例如在正常伤口愈合过程中、某些纤维化状态和血管异常的发展过程中，以及在某些癌症中，当恶性细胞变得更具攻击性、侵袭性和转移性时。源自三个胚胎胚层中任何一个的上皮细胞都可以经历 EMT，包括源自中胚层的上皮细胞，例如内皮细胞（有时称为 Endo-MT）和源自内胚层的上皮细胞，例如胎儿肝基质。在细胞水平上，EMT被定义为上皮细胞向间充质表型的转化，其特征是上皮标记物表达的减弱和间充质标记物的从头表达。这个过程是由细胞外因素诱导的，并且是可逆的，从而导致间充质到上皮细胞的转化（MET）。现在已经清楚，细胞可以同时表达上皮细胞和间充质的特性，并且这种过渡细胞类型驱动肿瘤细胞异质性，这是癌症进展、干细胞样细胞状态发展和耐药性的一个重要方面。在这里，我们回顾了一些证明胚胎发生过程中 EMT 存在的最早研究，并讨论了促进这一过程的细胞外因子和细胞内信号通路的发现，其中 TGFβ 信号超家族的成分发挥了重要作用。我们提到了围绕胚胎发育期间和成人疾病状态下的体内 EMT 的早期争议，以及该领域的成熟阶段，其中以 EMT 为目标来控制疾病状态是一个理想的目标。版权所有 © 2023 作者。由爱思唯尔有限公司出版。保留所有权利。

Epithelial-to-mesenchymal transition or transformation (EMT) is a cell shape-changing process that is utilized repeatedly throughout embryogenesis and is critical to the attainment of a precise body plan. In the adult, EMT is observed under both normal and pathological conditions, such as during normal wounding healing, during development of certain fibrotic states and vascular anomalies, as well as in some cancers when malignant cells progress to become more aggressive, invasive, and metastatic. Epithelia derived from any of the three embryonic germ layers can undergo EMT, including those derived from mesoderm, such as endothelial cells (sometimes termed Endo-MT) and those derived from endoderm such as fetal liver stroma. At the cellular level, EMT is defined as the transformation of epithelial cells towards a mesenchymal phenotype and is marked by attenuation of expression of epithelial markers and de novo expression of mesenchymal markers. This process is induced by extracellular factors and can be reversible, resulting in mesenchymal-to-epithelial transformation (MET). It is now clear that a cell can simultaneously express properties of both epithelia and mesenchyme, and that such transitional cell-types drive tumor cell heterogeneity, an important aspect of cancer progression, development of a stem-like cell state, and drug resistance. Here we review some of the earliest studies demonstrating the existence of EMT during embryogenesis and discuss the discovery of the extracellular factors and intracellular signaling pathways that contribute to this process, with components of the TGFβ signaling superfamily playing a prominent role. We mention early controversies surrounding in vivo EMT during embryonic development and in adult diseased states, and the maturation of the field to a stage wherein targeting EMT to control disease states is an aspirational goal.Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.