Regulation of Epithelial-Mesenchymal Transition by E3 Ubiquitin Ligases and Deubiquitinase in Cancer

Curr Cancer Drug Targets. 2016;16(2):110-8. doi: 10.2174/1568009616666151112122126.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Drug Design
  • Epithelial-Mesenchymal Transition* / drug effects
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy
  • Neoplasms / enzymology*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Stability
  • Proteolysis
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitin-Specific Proteases / genetics
  • Ubiquitin-Specific Proteases / metabolism*
  • Ubiquitination


  • Antineoplastic Agents
  • Transcription Factors
  • Ubiquitin-Protein Ligases
  • Ubiquitin-Specific Proteases
  • Proteasome Endopeptidase Complex