Inhibition of USP27X deubiquitinase destabilizes Snail1 renders breast and pancreas tumor cells sensitive to chemotherapy
Epithelial-to-mesenchymal transition (EMT) is controlled by a transcriptional factor called Snail1 in cancer cells. EMT is when epithelial cells lose their cell polarity and cell-cell adhesion, and gain migratory and invasive properties to become mesenchymal stem cells that can differentiate into a variety of cell types
Snail1 is short-lived in normal epithelial cells as a consequence of its coordinated and continuous ubiquitination by several F-box–specific E3 ligases. The degradation of Snail-1 by F-box–specific E3 ligases is prevented in cancer cells. The authors, based in in Spain and the US, identified USP27X as a deubiquitinase that stabilizes Snail1.
USP27X deubiquitinase depletion reduced Snail1-dependent cell migration and invasion and metastasis formation, increasing cellular sensitivity to cisplatin treatment. These results indicate that USP27X is an essential enzyme controlling Snail1 expression and function, opening up potential new therapeutic strategies for the inhibition of Snail1 expression and its protumoral actions.