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Title

A gene regulatory network to control EMT programs in development and disease

AuthorsFazilaty, Hassan; Rago, Luciano; Kass Youssef, Khalil; Ocaña, Oscar H.; Garcia-Asencio, Francisco; Arcas, Aída; Galcerán, Joan; Nieto, M. Ángela
Issue Date2019
PublisherSpringer Nature
CitationNature Communications 10: 5115 (2019)
AbstractThe Epithelial to Mesenchymal Transition (EMT) regulates cell plasticity during embryonic development and in disease. It is dynamically orchestrated by transcription factors (EMT-TFs), including Snail, Zeb, Twist and Prrx, all activated by TGF-β among other signals. Here we find that Snail1 and Prrx1, which respectively associate with gain or loss of stem-like properties and with bad or good prognosis in cancer patients, are expressed in complementary patterns during vertebrate development and in cancer. We show that this complementarity is established through a feedback loop in which Snail1 directly represses Prrx1, and Prrx1, through direct activation of the miR-15 family, attenuates the expression of Snail1. We also describe how this gene regulatory network can establish a hierarchical temporal expression of Snail1 and Prrx1 during EMT and validate its existence in vitro and in vivo, providing a mechanism to switch and select different EMT programs with important implications in development and disease.
Publisher version (URL)http://dx.doi.org/10.1038/s41467-019-13091-8
URIhttp://hdl.handle.net/10261/203222
Identifiersdoi: 10.1038/s41467-019-13091-8
issn: 2041-1723
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