Regulation of epithelial-mesenchymal transition through SUMOylation of transcription factors.

Carcinoma cells can transition from an epithelial-to-mesenchymal differentiation state through a process known as epithelial-mesenchymal transition (EMT). The process of EMT is characterized by alterations in the pattern of gene expression and is associated with a loss of cell polarity, an increase in invasiveness, and an increase in cells expressing cancer stem cell (CSC) markers. The reverse process of mesenchymal-to-epithelial transition (MET) can also occur, though the transitions characterizing EMT and MET can be incomplete. A growing number of transcription factors have been identified that influence the EMT/MET processes. Interestingly, SUMOylation regulates the functional activity of many of the transcription factors governing transitions between epithelial and mesenchymal states. In some cases, the transcription factor is a small ubiquitin-like modifier conjugated directly, thus altering its transcriptional activity or cell trafficking. In other cases, SUMOylation alters transcriptional mechanisms through secondary effects. This review explores the role of SUMOylation in controlling transcriptional mechanisms that regulate EMT/MET in cancer. Developing new drugs that specifically target SUMOylation offers a novel therapeutic approach to block tumor growth and metastasis. ©2014 American Association for Cancer Research.