School of Medicine, University of Western Australia (UWA), Harry Perkins Building, Fiona Stanley Hospital Campus, Robin Warren Drive, Murdoch, WA, 6150, Australia.
Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology (QUT), Brisbane, Australia.
Clin Exp Metastasis. 2018 Apr;35(4):285-308. doi: 10.1007/s10585-018-9906-x. Epub 2018 Jun 8.
Epithelial mesenchymal transition (EMT) describes the shift of cells from an epithelial form to a contact independent, migratory, mesenchymal form. In cancer the change is linked to invasion and metastasis. Tumour conditions, including hypoxia, acidosis and a range of treatments can trigger EMT, which is implicated in the subsequent development of resistance to those same treatments. Consequently, the degree to which EMT occurs may underpin the entire course of tumour progression and treatment response in a patient. In this review we look past the protective effect of EMT against the initial treatment, to the role of the mesenchymal state, once triggered, in promoting disease growth, spread and future treatment insensitivity. In patients a correlation was found between the propensity of a treatment to induce EMT and failure of that treatment to provide a survival benefit, implicating EMT induction in accelerated tumour progression after treatment cessation. Looking to the mechanisms driving this detrimental effect; increased proliferation, suppressed apoptosis, stem cell induction, augmented angiogenesis, enhanced metastatic dissemination, and immune tolerance, can all result from treatment-induced EMT and could worsen outcome. Evidence also suggests EMT induction with earlier therapies attenuates benefits of later treatments. Looking beyond epithelial tumours, de-differentiation also has therapy-attenuating effects and reversal thereof may yield similar rewards. A range of potential therapies are in development that may address the diverse mechanisms and molecular control systems involved in EMT-induced accelerated progression. Considering the broad reaching effects of mesenchymal shift identified, successful deployment of such treatments could substantially improve patient outcomes.
上皮间质转化（EMT）描述了细胞从上皮形式向无接触、迁移、间质形式的转变。在癌症中，这种变化与侵袭和转移有关。肿瘤条件，包括缺氧、酸中毒和一系列治疗方法，都可能引发 EMT，这与随后对这些相同治疗方法的耐药性发展有关。因此，EMT 发生的程度可能是患者肿瘤进展和治疗反应的整个过程的基础。在这篇综述中，我们不仅关注 EMT 对初始治疗的保护作用，还关注 EMT 一旦被触发后在促进疾病生长、扩散和未来治疗不敏感方面的作用。在患者中，发现治疗诱导 EMT 的倾向与该治疗未能提供生存益处之间存在相关性，这表明 EMT 诱导在治疗停止后加速肿瘤进展。从驱动这种有害影响的机制来看；增加增殖、抑制细胞凋亡、诱导干细胞、增强血管生成、增强转移扩散和免疫耐受，都可能是治疗诱导的 EMT 引起的，并可能导致预后恶化。有证据表明，早期治疗中的 EMT 诱导会降低后期治疗的益处。超越上皮肿瘤，去分化也有治疗减弱的效果，而逆转去分化可能会产生类似的回报。目前正在开发一系列潜在的治疗方法，可能针对 EMT 诱导的加速进展涉及的多种机制和分子控制系统。考虑到已经确定的间质转移的广泛影响，如果成功地应用这些治疗方法，可能会极大地改善患者的预后。
