The complex interplay between Notch signaling and Snail1 transcription factor in the regulation of epithelial–mesenchymal transition (EMT)
Notch and Snail1 in epithelial–mesenchymal transition (EMT)
Background: The epithelial–mesenchymal transition (EMT) is a highly coordinated process observed during embryonic development and adult tissue repair. It is characterized by the loss of cell–cell adhesion and apicobasal polarity, and the transition to a cell type with a spindle-like phenotype able to migrate through the basal membranes.
Methods: This review article includes available date from peer-reviewed publications associated with the role of Notch signaling and Snail1 transcription factor in activation and regulation of EMT.
Results: Growing evidences in the past few years demonstrated a significant role of Notch in EMT activation. It is not surprising because this pathway is the nexus of a unique and versatile signaling network, that regulates and is regulated by a variety of cellular mechanisms highly dependent on the biological context—especially tissue microenvironment. This compartment sends signals promoting and regulating EMT, which usually acts as a transcriptional repressors. Among them, Snail1 has been shown to be crucial for cellular movement during cancer progression and metastasis. In cancer patients, increased level of Snail1 is usually connected with poor clinical outcome, probably due to downregulation of E-cadherin expression. Moreover, the continuous expression of E-cadherin during developmental EMT in Snail1-deficient mouse embryos clearly supports the idea that its transcriptional repression is mostly related to Snail1 activity.
Conclusion: Cooperation of Notch signaling and Snail1 plays very significant role in such pathologies as wound healing and cancer development. Nevertheless, they are also involved in tissue embryonic development.
M. Brzozowa-Zasada, A. Piecuch, O. Segiet, Prof. K. Stęplewska, Prof. A. Gabriel, Prof. R. Wojnicz, European Surgery 5/2015