Epithelial-mesenchymal transition (EMT) plays an important role in the
development of tumor metastases by facilitating cell migration and invasion. One of
the hallmarks of EMT is the diminished expression of E-cadherin and gain of
mesenchymal traits, which are regulated by core EMT-inducing transcriptional
factors (EMT-TFs), such as Snail/Slug, ZEB1/ZEB2, and Twist1. EMT-TFs are
known to be extremely labile proteins, and their protein levels are tightly controlled
by the ubiquitin-proteasome system (UPS). Several E3 ubiquitin ligases have been shown to play crucial roles in the
regulation of EMT, and genetic aberrations and alterations in these ligases have been detected in human cancer. In this
review, we focused on EMT-TFs, describing the UPS controlling their activities and functions in cancer. A deeper
understanding of the role of UPS in the regulation of EMT will provide valuable information for the development of
effective anti-metastatic drugs to modulate the malignant processes mediated by EMT.
Keywords: Deubiquitinase (DUB), E3 ubiquitin ligase, epithelial-mesenchymal transition (EMT), Snail, Slug, Twist, ubiquitinproteasome
system (UPS), ZEB.
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