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- Title
A gene regulatory network to control EMT programs in development and disease.
- Authors
Fazilaty, Hassan; Rago, Luciano; Kass Youssef, Khalil; Ocaña, Oscar H.; Garcia-Asencio, Francisco; Arcas, Aida; Galceran, Juan; Nieto, M. Angela
- 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. EMT is a developmental process that is aberrantly activated in metastasizing cancer cells, but how multiple transcription factors regulate EMT is unclear. Here, the authors uncover a gene regulatory network between Prrx1 and Snail1 that selects EMT mode in developing vertebrates and cancer cells.
- Subjects
GENE regulatory networks; EMBRYOLOGY; EPITHELIAL cells; MESENCHYMAL stem cells; TRANSCRIPTION factors; CANCER cells
- Publication
Nature Communications, 2019, Vol 10, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-019-13091-8