Transcriptional regulation of cell polarity in EMT and cancer

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. © 2008 Macmillan Publishers Limited All rights reserved.
Our work is supported by grants from the Spanish Ministry of Education and Science (SAF2007-63051, NAN2004-09230-C04 and CONSOLIDER-INGENIO 2010 CSD2007-00017 to AC, and SAF2007-63075 to GMB), the EU (MRTN-CT-2004- 005428) to AC and from the Fundación Mutua Madrileña (2006) to GMB.GMB is a junior researcher contracted on the Ramon y Cajal program, 2004.