title: Twist1-positive epithelial cells retain adhesive and proliferative capacity throughout dissemination.
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.
authors.affiliation: Departments of Cell Biology and Oncology, Center for Cell Dynamics, Johns Hopkins University School of Medicine, 855 N. Wolfe St, Baltimore, MD 21205, USA.
authors.forename: Eliah R
authors.initials: ER
authors.lastname: Shamir
authors.affiliation: Departments of Cell Biology and Oncology, Center for Cell Dynamics, Johns Hopkins University School of Medicine, 855 N. Wolfe St, Baltimore, MD 21205, USA Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, MS Donner, Berkeley, CA 94720, USA.
authors.forename: Kester
authors.initials: K
authors.lastname: Coutinho
authors.affiliation: Departments of Cell Biology and Oncology, Center for Cell Dynamics, Johns Hopkins University School of Medicine, 855 N. Wolfe St, Baltimore, MD 21205, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Georgess
authors.affiliation: Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, MS Donner, Berkeley, CA 94720, USA.
authors.forename: Manfred
authors.initials: M
authors.lastname: Auer
authors.affiliation: Departments of Cell Biology and Oncology, Center for Cell Dynamics, Johns Hopkins University School of Medicine, 855 N. Wolfe St, Baltimore, MD 21205, USA aewald2@jhmi.edu.
authors.forename: Andrew J
authors.identifier: http://orcid.org/0000-0002-1964-0740
authors.initials: AJ
authors.lastname: Ewald
keywords: Cell migration; Dissemination; Epithelial-mesenchymal transition; Intercellular junctions; Proteolysis; Twist1