Twist1-positive epithelial cells retain adhesive and proliferative capacity throughout dissemination

Eliah R. Shamir, Kester Coutinho, Dan Georgess, Manfred Auer, Andrew J. Ewald

Research output: Contribution to journalArticle

Abstract

Dissemination is the process by which cells detach and migrate away from a multicellular tissue. The epithelial-to-mesenchymal transition (EMT) conceptualizes dissemination in a stepwise fashion, with downregulation of E-cadherin leading to loss of intercellular junctions, induction of motility, and then escape from the epithelium. This gain of migratory activity is proposed to be mutually exclusive with proliferation. We previously developed a dissemination assay based on inducible expression of the transcription factor Twist1 and here utilize it to characterize the timing and dynamics of intercellular adhesion, proliferation and migration during dissemination. Surprisingly, Twist1+ epithelium displayed extensive intercellular junctions, and Twist1- luminal epithelial cells could still adhere to disseminating Twist1+ cells. Although proteolysis and proliferation were both observed throughout dissemination, neither was absolutely required. Finally, Twist1+ cells exhibited a hybrid migration mode; their morphology and nuclear deformation were characteristic of amoeboid cells, whereas their dynamic protrusive activity, pericellular proteolysis and migration speeds were more typical of mesenchymal cells. Our data reveal that epithelial cells can disseminate while retaining competence to adhere and proliferate.

Original languageEnglish (US)
Pages (from-to)1216-1228
Number of pages13
JournalBiology Open
Volume5
Issue number9
DOIs
StatePublished - Sep 15 2016

Keywords

  • Cell migration
  • Dissemination
  • Epithelial-mesenchymal transition
  • Intercellular junctions
  • Proteolysis
  • Twist1

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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