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Tytuł:
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A gene regulatory network to control EMT programs in development and disease.
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Autorzy:
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Fazilaty, Hassan
Rago, Luciano
Kass Youssef, Khalil
Ocaña, Oscar H.
Garcia-Asencio, Francisco
Arcas, Aida
Galceran, Juan
Nieto, M. Angela
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Temat:
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GENE regulatory networks
EMBRYOLOGY
EPITHELIAL cells
MESENCHYMAL stem cells
TRANSCRIPTION factors
CANCER cells
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Źródło:
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Nature Communications; 11/11/2019, Vol. 10 Issue 1, p1-16, 16p
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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. [ABSTRACT FROM AUTHOR]
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