Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance
- PMID: 26560033
- PMCID: PMC4662610
- DOI: 10.1038/nature15748
Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance
Abstract
The role of epithelial-to-mesenchymal transition (EMT) in metastasis is a longstanding source of debate, largely owing to an inability to monitor transient and reversible EMT phenotypes in vivo. Here we establish an EMT lineage-tracing system to monitor this process in mice, using a mesenchymal-specific Cre-mediated fluorescent marker switch system in spontaneous breast-to-lung metastasis models. We show that within a predominantly epithelial primary tumour, a small proportion of tumour cells undergo EMT. Notably, lung metastases mainly consist of non-EMT tumour cells that maintain their epithelial phenotype. Inhibiting EMT by overexpressing the microRNA miR-200 does not affect lung metastasis development. However, EMT cells significantly contribute to recurrent lung metastasis formation after chemotherapy. These cells survived cyclophosphamide treatment owing to reduced proliferation, apoptotic tolerance and increased expression of chemoresistance-related genes. Overexpression of miR-200 abrogated this resistance. This study suggests the potential of an EMT-targeting strategy, in conjunction with conventional chemotherapies, for breast cancer treatment.
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Comment in
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Cell fate: Transition loses its invasive edge.Nature. 2015 Nov 26;527(7579):452-3. doi: 10.1038/nature16313. Epub 2015 Nov 11. Nature. 2015. PMID: 26560026 No abstract available.
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Transition to resistance: An unexpected role of the EMT in cancer chemoresistance.Genes Dis. 2016 Mar;3(1):3-6. doi: 10.1016/j.gendis.2016.01.002. Epub 2016 Jan 28. Genes Dis. 2016. PMID: 28491932 Free PMC article.
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Just How Critical is Epithelial-to-Mesenchymal Transition (EMT) to Metastatic Dissemination?J Pharmacol Clin Trials. 2019;1(1):8-10. doi: 10.29199/jpct.101015. J Pharmacol Clin Trials. 2019. PMID: 32864664 Free PMC article. No abstract available.
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