Canonical BMP signaling executes epithelial-mesenchymal transition downstream of SNAIL1

Abstract: Epithelial-mesenchymal transition (EMT) is a pivotal process in development and disease. In carcinogenesis, various signaling pathways are known to trigger EMT by inducing the expression of EMT transcription factors (EMT-TFs) like SNAIL1, ultimately promoting invasion, metastasis and chemoresistance. However, how EMT is executed downstream of EMT-TFs is incompletely understood. Here, using human colorectal cancer (CRC) and mammary cell line models of EMT, we demonstrate that SNAIL1 critically relies on bone morphogenetic protein (BMP) signaling for EMT execution. This activity requires the transcription factor SMAD4 common to BMP/TGFβ pathways, but is TGFβ signaling-independent. Further, we define a signature of BMP-dependent genes in the EMT-transcriptome, which orchestrate EMT-induced invasiveness, and are found to be regulated in human CRC transcriptomes and in developmental EMT processes. Collectively, our findings substantially augment the knowledge of mechanistic routes whereby EMT can be effectuated, which is relevant for the conceptual understanding and therapeutic targeting of EMT processes

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch
Anmerkungen
Cancers. - 12, 4 (2020) , 1019, ISSN: 2072-6694

Schlagwort
Knochen-Morphogenese-Proteine
Smad-Proteine
Dickdarmtumor
Bauchspeicheldrüsentumor
Invasion
Metastase

Ereignis
Veröffentlichung
(wo)
Freiburg
(wer)
Universität
(wann)
2020

DOI
10.3390/cancers12041019
URN
urn:nbn:de:bsz:25-freidok-1659451
Rechteinformation
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Letzte Aktualisierung
25.03.2025, 13:51 MEZ

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Entstanden

  • 2020

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