Program in Molecular Biology, Medical Scientist Training Program, University of Colorado School of Medicine, Aurora CO 80045, USA.
Future Oncol. 2009 Oct;5(8):1129-43. doi: 10.2217/fon.09.94.
The epithelial-mesenchymal transition (EMT) is a critical developmental process from the earliest events of embryogenesis to later morphogenesis and organ formation. EMT contributes to the complex architecture of the embryo by permitting the progression of embryogenesis from a simple single-cell layer epithelium to a complex three-dimensional organism composed of both epithelial and mesenchymal cells. However, in most tissues EMT is a developmentally restricted process and fully differentiated epithelia typically maintain their epithelial phenotype. Recently, elements of EMT, specifically the loss of epithelial markers and the gain of mesenchymal markers, have been observed in pathological states, including epithelial cancers. Analysis of the molecular mechanisms of this oncogenic epithelial plasticity have implicated the inappropriate expression and activation of developmental EMT programs, suggesting that cancer cells may reinstitute properties of developmental EMT including enhanced migration and invasion. Thus, in the context of cancer, an EMT-like process may permit dissemination of tumor cells from the primary tumor into the surrounding stroma, setting the stage for metastatic spread. Consistent with this hypothesis, activation of these developmental EMT programs in human cancer correlates with advanced disease and poor prognosis. This review will focus on the current knowledge regarding developmental EMT pathways that have been implicated in cancer progression.
上皮-间充质转化（EMT）是从胚胎发生的最早事件到后期形态发生和器官形成的关键发育过程。EMT 通过允许胚胎发生从简单的单细胞层上皮进展为由上皮细胞和间充质细胞组成的复杂三维生物体，为胚胎的复杂结构做出贡献。然而，在大多数组织中，EMT 是一种发育受限的过程，通常完全分化的上皮细胞保持其上皮表型。最近，在包括上皮癌在内的病理状态下观察到 EMT 的特定元素，特别是上皮标志物的丧失和间充质标志物的获得。对这种致癌上皮可塑性的分子机制的分析表明，发育性 EMT 程序的不当表达和激活，表明癌细胞可能重新建立发育性 EMT 的特性，包括增强的迁移和侵袭。因此，在癌症的背景下，EMT 样过程可能允许肿瘤细胞从原发性肿瘤扩散到周围基质，为转移扩散奠定基础。与该假说一致，在人类癌症中激活这些发育性 EMT 程序与晚期疾病和预后不良相关。这篇综述将重点介绍与癌症进展相关的发育性 EMT 途径的最新知识。
