Key Points
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Transitions between epithelial and mesenchymal states underlie epithelial cell plasticity and contribute to tumour progression and intratumoural heterogeneity.
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The epithelial–mesenchymal transition (EMT) is triggered by a diverse set of stimuli including growth factor signalling, tumour–stromal cell interactions and hypoxia. There is a significant crosstalk among EMT-inducing signals and transcription factors that can lead to stable reprogramming of epithelial cells to mesenchymal states.
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EMT has been shown to result in cancer cells with stem cell-like characteristics that have a propensity to invade surrounding tissue and display resistance to certain therapeutic interventions.
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The mesenchymal–epithelial transition (MET) may have a role in the reversion of disseminated mesenchymal tumour cells to a more epithelial state in distant metastases.
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microRNAs have been identified as a new class of EMT regulators, in part owing to their regulation of EMT-inducing transcription factors.
Abstract
Transitions between epithelial and mesenchymal states have crucial roles in embryonic development. Emerging data suggest a role for these processes in regulating cellular plasticity in normal adult tissues and in tumours, where they can generate multiple, distinct cellular subpopulations contributing to intratumoural heterogeneity. Some of these subpopulations may exhibit more differentiated features, whereas others have characteristics of stem cells. Owing to the importance of these tumour-associated phenotypes in metastasis and cancer-related mortality, targeting the products of such cellular plasticity is an attractive but challenging approach that is likely to lead to improved clinical management of cancer patients.
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Acknowledgements
We thank members of our laboratories for their critical reading of this manuscript and useful discussions. Research related to EMT in our laboratories is supported by National Institute of Health P50 CA89393 and PO1 CA80111 (K.P. and R.A.W.), U54 CA 126515 (R.A.W.), DoD Breast Cancer Research Program W81XWH-07-1-0294 (K.P.) and BC073843 (R.A.W.), American Cancer Society RSG-05-154-01-MGO (K.P.), Breast Cancer Research Foundation (K.P. and R.A.W.), Ludwig Fund for Cancer Research (R.A.W.), and the Advanced Medical Research Foundation (R.A.W.). R.A.W. is an American Cancer Society Research Professor and a Daniel K. Ludwig Cancer Research Professor.
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Kornelia Polyak receives research funding and is a consultant to Novartis
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Polyak, K., Weinberg, R. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer 9, 265–273 (2009). https://doi.org/10.1038/nrc2620
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DOI: https://doi.org/10.1038/nrc2620
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