Ubiquitination and deubiquitination in the regulation of epithelial-mesenchymal transition in cancer: Shifting gears at the molecular level.

The process of conversion of non-motile epithelial cells to their motile mesenchymal counterparts is known as epithelial-mesenchymal transition (EMT), which is a fundamental event during embryonic development, tissue repair, and for the maintenance of stemness. However, this crucial process is hijacked in cancer and becomes the means by which cancer cells acquire further malignant properties such as increased invasiveness, acquisition of stem cell-like properties, increased chemoresistance, and immune evasion ability. The switch from epithelial to mesenchymal phenotype is mediated by a wide variety of effector molecules such as transcription factors, epigenetic modifiers, post-transcriptional and post-translational modifiers. Ubiquitination and de-ubiquitination are two post-translational processes that are fundamental to the ubiquitin-proteasome system (UPS) of the cell, and the shift in equilibrium between these two processes during cancer dictates the suppression or activation of different intracellular processes, including EMT. Here, we discuss the complex and dynamic relationship between components of the UPS and EMT in cancer.