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

Hassan Fazilaty, Luciano Rago, Khalil Kass Youssef, Oscar H. Ocaña, Francisco Garcia-Asencio, Aida Arcas, Juan Galceran and M. Angela Nieto ()
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Hassan Fazilaty: Avda. Ramón y Cajal s/n, Sant Joan d’
Luciano Rago: Avda. Ramón y Cajal s/n, Sant Joan d’
Khalil Kass Youssef: Avda. Ramón y Cajal s/n, Sant Joan d’
Oscar H. Ocaña: Avda. Ramón y Cajal s/n, Sant Joan d’
Francisco Garcia-Asencio: Avda. Ramón y Cajal s/n, Sant Joan d’
Aida Arcas: Avda. Ramón y Cajal s/n, Sant Joan d’
Juan Galceran: Avda. Ramón y Cajal s/n, Sant Joan d’
M. Angela Nieto: Avda. Ramón y Cajal s/n, Sant Joan d’

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: Abstract The 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.

Date: 2019
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13091-8

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DOI: 10.1038/s41467-019-13091-8

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