- [GENE THERAPY AND REGULATION OF GENE EXPRESSION]
- [CANCER GENE THERAPY]
- [NON-CODING RNA AND REGULATION OF THE CANCER GENOME]
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, M Angela Nieto
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.
CITATION Nat Commun. 2019 Nov 11;10(1):5115. doi: 10.1038/s41467-019-13091-8.