Localized translation regulates cell adhesion and transendothelial migration

J Cell Sci. 2016 Nov 1;129(21):4105-4117. doi: 10.1242/jcs.191320. Epub 2016 Sep 16.

Abstract

Epithelial-to-mesenchymal transition (EMT) is a process by which cancer cells gain the ability to leave the primary tumor site and invade surrounding tissues. These metastatic cancer cells can further increase their plasticity by adopting an amoeboid-like morphology, by undergoing mesenchymal-to-amoeboid transition (MAT). We found that adhering cells produce spreading initiation centers (SICs), transient structures that are localized above nascent adhesion complexes, and 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 recapitulates events that are associated with amoeboid-to-mesenchymal transition (AMT). We found that polyadenylated RNAs are enriched within SICs, blocking their translation decreased adhesion potential of metastatic cells that progressed through EMT. These results point to a so-far-unknown checkpoint that regulates cell adhesion and allows metastatic cells to alter adhesion strength to modulate their dissemination.

Keywords: AMT; Amoeboid-to-mesenchymal transition; EMT; Epithelial cells; Epithelial-to-mesenchymal transition; Focal adhesion; Invasion; MAT; Mesenchymal cells; Mesenchymal-to-amoeboid transition; RNA-binding proteins; SICs; Spreading initiation centers; Translation regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Shape
  • Enzyme Activation
  • Epithelial-Mesenchymal Transition
  • Focal Adhesions / metabolism
  • GTP Phosphohydrolases / metabolism
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Mesoderm / metabolism
  • Models, Biological
  • Neoplasm Metastasis
  • Polyadenylation
  • Protein Biosynthesis*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / metabolism
  • Transendothelial and Transepithelial Migration*

Substances

  • RNA, Messenger
  • RNA-Binding Proteins
  • GTP Phosphohydrolases

Grants and funding