Puisieux Alain
Centre Léon Bérard, Lyon, F-69008, France.
Bull Acad Natl Med. 2009 Dec;193(9):2017-32; discussion 2032-4.
During epithelial-mesenchymal transition (EMT)--a morphogenetic program involved in several steps of embryogenesis--epithelial cells lose many of their epithelial characteristics and acquire properties typical of mesenchymal cells. The mechanisms underlying this transition are frequently reactivated during tumor progression, generating cells with enhanced motility and invasiveness. Several in vitro and in vivo studies point to a role of EMT in metastatic dissemination of epithelial tumors. In addition, recent data show that EMT-inducing transcription factors, such as the Twist proteins, can inhibit crucial oncosuppressive responses that normally counteract the emergence of a cell population with aberrant mitogenic activity, by triggering either apoptosis or premature senescence. Abrogation of these failsafe cellular mechanisms is a prerequisite for malignant progression. Together, these observations suggest that EMT could play a major pathological role by favoring both tumor development and metastatic dissemination. We examine the main data supporting this hypothesis and discuss its potential clinical implications.
在上皮-间质转化（EMT）过程中——这是一种参与胚胎发育多个步骤的形态发生程序——上皮细胞失去了许多上皮特征，并获得了间充质细胞的典型特性。这种转化背后的机制在肿瘤进展过程中经常被重新激活，产生具有更强运动性和侵袭性的细胞。多项体外和体内研究表明EMT在上皮性肿瘤的转移扩散中发挥作用。此外，最近的数据显示，诱导EMT的转录因子，如Twist蛋白，可通过触发凋亡或过早衰老来抑制关键的肿瘤抑制反应，这些反应通常会对抗具有异常促有丝分裂活性的细胞群体的出现。废除这些故障保护细胞机制是恶性进展的先决条件。综上所述，这些观察结果表明，EMT可能通过促进肿瘤发展和转移扩散而发挥主要病理作用。我们研究了支持这一假设的主要数据，并讨论了其潜在的临床意义。
