Abstract
Embryonic development requires the acquisition of a mesenchymal migratory phenotype by some epithelial cells in strictly spatio-temporal regulated fashion during organ formation. Interestingly, this epithelial-to mesenchymal transition (EMT) process is aberrantly activated during tumor progression. The reverse mesenchymal-to epithelial transition (MET) process is, nevertheless, required for development of metastatic foci, implying a highly dynamic regulation of epithelial plasticity. The expression of different transcription factors (called EMT-TFs) activates this reversible complex program although its regulation remains partially elusive. Recently, non-coding microRNAs have emerged as novel regulators of cell differentiation by targeting EMT-TFs and other molecules involved in tumor progression. In this chapter, we will discuss the different mechanisms used by these microRNAs to regulate epithelial plasticity of tumor cells during tumor progression and metastasis. We will pay particular attention to two negative feedback pathways involving miR-200/ZEB1 and p53/miR-34/SNAIL1 that clearly shows the plasticity and interconnectivity of the EMT and MET programs. Remarkably, recent studies showed that certain microRNAs might be used in the diagnostic and treatment of cancer providing new therapeutic opportunities to combat tumor progression and increase patient survival.
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Acknowledgements
Research of A. Cano group is funded by the Spanish Ministry of Science and Innovation (SAF2010-21143; Consolider CSD2007/0007). ADL is supported by a Sara Borrell contract from the Instituto de Salud Carlos III (ISCIII).
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Díaz-López, A., Cano, A. (2014). Epithelial Plasticity Regulation by MicroRNAs. In: Hayat, M. (eds) Stem Cells and Cancer Stem Cells, Volume 12. Stem Cells and Cancer Stem Cells, vol 12. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-8032-2_17
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DOI: https://doi.org/10.1007/978-94-017-8032-2_17
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