Localized translation regulates cell adhesion and transendothelial migration

Abstract

By progressing through the epithelial to mesenchymal transition (EMT), cancer cells gain the ability to leave the primary tumor site and invade surrounding tissues. These metastatic cancers cells can further increase their plasticity by adopting an amoeboid-like morphology, by undergoing mesenchymal to amoeboid transition (MAT). We found that adhering cells producing spreading initiation centers (SIC), a transient structure localized above nascent adhesion complexes, share common biological and morphological characteristics associated with amoeboid cells. Meanwhile, spreading cells seem to return to a mesenchymal-like morphology. Thus, our results indicate that SIC-induced adhesion recapitulate events associated with amoeboid to mesenchymal transition (AMT). We found that polyadenylated RNAs were enriched within SIC and blocking their translation decreased adhesion potential of metastatic cells that progressed through EMT. These results point to a novel checkpoint regulating cell adhesion and allowing metastatic cells to alter adhesion strength in order to modulate their dissemination.