PUBLICATION
A gene regulatory network to control EMT programs in development and disease
- Authors
- Fazilaty, H., Rago, L., Kass Youssef, K., Ocaña, O.H., Garcia-Asencio, F., Arcas, A., Galceran, J., Nieto, M.A.
- ID
- ZDB-PUB-200229-21
- Date
- 2019
- Source
- Nature communications 10: 5115 (Journal)
- Registered Authors
- Fazilaty, Hassan, Galceran, Juan, Nieto, Angela, Ocaña, Oscar H., Rago, Luciano
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Line
- Chick Embryo
- Epithelial-Mesenchymal Transition/genetics*
- Gene Regulatory Networks*
- Genetic Predisposition to Disease
- Homeodomain Proteins
- Humans
- Mice, Inbred C57BL
- MicroRNAs/metabolism
- Prognosis
- Promoter Regions, Genetic
- Snail Family Transcription Factors/metabolism
- Zebrafish/embryology
- PubMed
- 31712603 Full text @ Nat. Commun.
Citation
Fazilaty, H., Rago, L., Kass Youssef, K., Ocaña, O.H., Garcia-Asencio, F., Arcas, A., Galceran, J., Nieto, M.A. (2019) A gene regulatory network to control EMT programs in development and disease. Nature communications. 10:5115.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping