Abstract
Epithelial-mesenchymal transition (EMT) is implicated in converting stationary epithelial tumor cells into motile mesenchymal cells during metastasis. However, the involvement of EMT in metastasis is still controversial, due to the lack of a mesenchymal phenotype in human carcinoma metastases. Using a spontaneous squamous cell carcinoma mouse model, we show that activation of the EMT-inducing transcription factor Twist1 is sufficient to promote carcinoma cells to undergo EMT and disseminate into blood circulation. Importantly, in distant sites, turning off Twist1 to allow reversion of EMT is essential for disseminated tumor cells to proliferate and form metastases. Our study demonstrates in vivo the requirement of "reversible EMT" in tumor metastasis and may resolve the controversy on the importance of EMT in carcinoma metastasis.
Copyright © 2012 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Breast Neoplasms / genetics
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology*
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Carcinoma, Squamous Cell / genetics
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Carcinoma, Squamous Cell / metabolism
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Carcinoma, Squamous Cell / pathology*
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Carcinoma, Squamous Cell / secondary
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Cell Proliferation
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Epithelial Cells / metabolism
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Epithelial Cells / pathology
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Epithelial-Mesenchymal Transition / genetics
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Epithelial-Mesenchymal Transition / physiology*
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Female
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Humans
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Lung Neoplasms / genetics
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology
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Lung Neoplasms / secondary*
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Mice
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Neoplasm Invasiveness
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Neoplasm Metastasis
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Twist-Related Protein 1 / genetics
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Twist-Related Protein 1 / metabolism
Substances
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Nuclear Proteins
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TWIST1 protein, human
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Transcription Factors
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Twist-Related Protein 1