Moreno-Bueno G, Portillo F, Cano A
Departamento de Bioquímica, Universidad Autónoma de Madrid, Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain.
Oncogene. 2008 Nov 24;27(55):6958-69. doi: 10.1038/onc.2008.346.
The epithelial-to-mesenchymal transition (EMT) is a crucial process in tumour progression providing tumour cells with the ability to escape from the primary tumour, to migrate to distant regions and to invade tissues. EMT requires a loss of cell-cell adhesion and apical-basal polarity, as well as the acquisition of a fibroblastoid motile phenotype. Several transcription factors have emerged in recent years that induce EMT, with important implications for tumour progression. However, their effects on cell polarity remain unclear. Here, we have re-examined the data available related to the effect of EMT related transcription factors on epithelial cell plasticity, focusing on their impact on cell polarity. Transcriptional and post-transcriptional regulatory mechanisms mediated by several inducers of EMT, in particular the ZEB and Snail factors, downregulate the expression and/or functional organization of core polarity complexes. We also summarize data on the expression of cell polarity genes in human tumours and analyse genetic interactions that highlight the existence of complex regulatory networks converging on the regulation of cell polarity by EMT inducers in human breast carcinomas. These recent observations provide new insights into the relationship between alterations in cell polarity components and EMT in cancer, opening new avenues for their potential use as therapeutic targets to prevent tumour progression.
上皮-间质转化（EMT）是肿瘤进展过程中的一个关键过程，它赋予肿瘤细胞逃离原发肿瘤、迁移至远处区域并侵袭组织的能力。EMT需要细胞间黏附丧失和顶端-基底端极性丧失，以及获得成纤维样运动表型。近年来出现了几种诱导EMT的转录因子，它们对肿瘤进展具有重要影响。然而，它们对细胞极性的影响仍不清楚。在此，我们重新审视了与EMT相关转录因子对上皮细胞可塑性影响的现有数据，重点关注它们对细胞极性的影响。由几种EMT诱导剂介导的转录和转录后调控机制，特别是ZEB和Snail因子，下调了核心极性复合物的表达和/或功能组织。我们还总结了人类肿瘤中细胞极性基因表达的数据，并分析了遗传相互作用，这些相互作用突出了在人类乳腺癌中存在复杂调控网络，这些网络汇聚于EMT诱导剂对细胞极性的调控。这些最新观察结果为癌症中细胞极性成分改变与EMT之间的关系提供了新见解，为它们作为预防肿瘤进展的治疗靶点的潜在应用开辟了新途径。
