Abstract
The epithelial-mesenchymal plasticity (EMP) is a process by which epithelial cells acquire the ability to dynamically switch between epithelial and mesenchymal phenotypic cellular states. Epithelial cell plasticity in the context of an epithelial-to-mesenchymal transition (EMT) confers increased cell motility, invasiveness and the ability to disseminate to distant sites and form metastasis. The modulation of molecularly defined targets involved in this process has become an attractive therapeutic strategy against cancer. Protein degradation carried out by ubiquitination has gained attention as it can selectively degrade proteins of interest. In the ubiquitination reaction, the E3 ubiquitin-ligases are responsible for the specific binding of ubiquitin to a small subset of target proteins, and are considered promising anticancer drug targets. In this review, we summarize the role of the E3 ubiquitin-ligases that control targeted protein degradation in cancer-EMT, and we highlight the potential use of the E3 ubiquitin-ligases as drug targets for the development of small-molecule drugs against cancer.
Highlights
Epithelial–mesenchymal plasticity (EMP) is an important reversible program characterized by the ability of epithelial cells to dynamically switch between different phenotypic cellular states.This process encompasses the epithelial–mesenchymal transition and the mesenchymal–epithelial transition, bearing important implication for tumor progression and metastasis, therapeutic resistanceCancers 2020, 12, 3093; doi:10.3390/cancers12113093 www.mdpi.com/journal/cancersCancers 2020, 12, 3093 and cancer stem cell properties [1]
We focus on the regulation of the cancer-epithelial–mesenchymal plasticity (EMP) by targeted protein degradation induced through ubiquitination, a post-translational modification that regulates protein turnover
Around 90% of cancer-deaths are due to metastasis, a multistep process that enables primary tumors to disseminate, invade and colonize distant organs
Summary
Epithelial–mesenchymal plasticity (EMP) is an important reversible program characterized by the ability of epithelial cells to dynamically switch between different phenotypic cellular states. This process encompasses the epithelial–mesenchymal transition and the mesenchymal–epithelial transition, bearing important implication for tumor progression and metastasis, therapeutic resistance. We focus on the regulation of the cancer-EMP by targeted protein degradation induced through ubiquitination, a post-translational modification that regulates protein turnover. We highlight the crucial role of the E3 ubiquitin-ligases in cancer-EMP, enzymes responsible for the recognition of specific target proteins targeted for degradation. We highlight the potential use of the E3 ubiquitin-ligases as promising drug targets for the development of small molecule drugs against cancer
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