New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer

doi:10.1038/s41580-018-0080-4

Review

. 2019 Feb;20(2):69-84.

doi: 10.1038/s41580-018-0080-4.

New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer

Anushka Dongre¹, Robert A Weinberg^{2

3

4}

Affiliations

¹ Whitehead Institute for Biomedical Research, Cambridge, MA, USA.
² Whitehead Institute for Biomedical Research, Cambridge, MA, USA. weinberg@wi.mit.edu.
³ MIT Ludwig Center for Molecular Oncology, Cambridge, MA, USA. weinberg@wi.mit.edu.
⁴ Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. weinberg@wi.mit.edu.

PMID: 30459476
DOI: 10.1038/s41580-018-0080-4

Review

New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer

Anushka Dongre et al. Nat Rev Mol Cell Biol. 2019 Feb.

. 2019 Feb;20(2):69-84.

doi: 10.1038/s41580-018-0080-4.

Authors

Anushka Dongre¹, Robert A Weinberg^{2

3

4}

Affiliations

¹ Whitehead Institute for Biomedical Research, Cambridge, MA, USA.
² Whitehead Institute for Biomedical Research, Cambridge, MA, USA. weinberg@wi.mit.edu.
³ MIT Ludwig Center for Molecular Oncology, Cambridge, MA, USA. weinberg@wi.mit.edu.
⁴ Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. weinberg@wi.mit.edu.

PMID: 30459476
DOI: 10.1038/s41580-018-0080-4

Abstract

Epithelial-mesenchymal transition (EMT) is a cellular programme that is known to be crucial for embryogenesis, wound healing and malignant progression. During EMT, cell-cell and cell-extracellular matrix interactions are remodelled, which leads to the detachment of epithelial cells from each other and the underlying basement membrane, and a new transcriptional programme is activated to promote the mesenchymal fate. In the context of neoplasias, EMT confers on cancer cells increased tumour-initiating and metastatic potential and a greater resistance to elimination by several therapeutic regimens. In this Review, we discuss recent findings on the mechanisms and roles of EMT in normal and neoplastic tissues, and the cell-intrinsic signals that sustain expression of this programme. We also highlight how EMT gives rise to a variety of intermediate cell states between the epithelial and the mesenchymal state, which could function as cancer stem cells. In addition, we describe the contributions of the tumour microenvironment in inducing EMT and the effects of EMT on the immunobiology of carcinomas.

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References

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[1] Nieto, M. A. Epithelial–mesenchymal transitions in development and disease: old views and new perspectives. Int. J. Dev. Biol. 53, 1541–1547 (2009). - PubMed

[2] Nieto, M. A. Epithelial–mesenchymal transitions in development and disease: old views and new perspectives. Int. J. Dev. Biol. 53, 1541–1547 (2009). - PubMed

[3] Nieto, M. A., Huang, R. Y., Jackson, R. A. & Thiery, J. P. EMT: 2016. Cell 166, 21–45 (2016). - DOI

[4] Nieto, M. A., Huang, R. Y., Jackson, R. A. & Thiery, J. P. EMT: 2016. Cell 166, 21–45 (2016). - DOI

[5] Kalluri, R. & Weinberg, R. A. The basics of epithelial–mesenchymal transition. J. Clin. Invest. 119, 1420–1428 (2009). - PubMed - PMC

[6] Kalluri, R. & Weinberg, R. A. The basics of epithelial–mesenchymal transition. J. Clin. Invest. 119, 1420–1428 (2009). - PubMed - PMC

[7] Thiery, J. P., Acloque, H., Huang, R. Y. & Nieto, M. A. Epithelial–mesenchymal transitions in development and disease. Cell 139, 871–890 (2009).

[8] Thiery, J. P., Acloque, H., Huang, R. Y. & Nieto, M. A. Epithelial–mesenchymal transitions in development and disease. Cell 139, 871–890 (2009).

[9] Ye, X. et al. Distinct EMT programs control normal mammary stem cells and tumour-initiating cells. Nature 525, 256–260 (2015). - PubMed - PMC

[10] Ye, X. et al. Distinct EMT programs control normal mammary stem cells and tumour-initiating cells. Nature 525, 256–260 (2015). - PubMed - PMC

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New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer

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New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer

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