Unjamming overcomes kinetic and proliferation arrest in terminally differentiated cells and promotes collective motility of carcinoma

Andrea Palamidessi, Chiara Malinverno, Emanuela Frittoli, Salvatore Corallino, Elisa Barbieri, Sara Sigismund, Galina V. Beznoussenko, Emanuele Martini, Massimiliano Garre, Ines Ferrara, Claudio Tripodo, Flora Ascione, Elisabetta A. Cavalcanti-Adam, Qingsen Li, Pier Paolo Di Fiore, Dario Parazzoli, Fabio Giavazzi, Roberto Cerbino, Giorgio Scita

Research output: Contribution to journalArticlepeer-review

Abstract

During wound repair, branching morphogenesis and carcinoma dissemination, cellular rearrangements are fostered by a solid-to-liquid transition, known as unjamming. The biomolecular machinery behind unjamming and its pathophysiological relevance remain, however, unclear. Here, we study unjamming in a variety of normal and tumorigenic epithelial two-dimensional (2D) and 3D collectives. Biologically, the increased level of the small GTPase RAB5A sparks unjamming by promoting non-clathrin-dependent internalization of epidermal growth factor receptor that leads to hyperactivation of the kinase ERK1/2 and phosphorylation of the actin nucleator WAVE2. This cascade triggers collective motility effects with striking biophysical consequences. Specifically, unjamming in tumour spheroids is accompanied by persistent and coordinated rotations that progressively remodel the extracellular matrix, while simultaneously fluidizing cells at the periphery. This concurrent action results in collective invasion, supporting the concept that the endo-ERK1/2 pathway is a physicochemical switch to initiate collective invasion and dissemination of otherwise jammed carcinoma.

Original languageEnglish
Pages (from-to)1252-1263
Number of pages12
JournalNature Materials
Volume18
Issue number11
DOIs
Publication statusPublished - Nov 1 2019

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanics of Materials
  • Mechanical Engineering

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