TY - JOUR
T1 - Unjamming overcomes kinetic and proliferation arrest in terminally differentiated cells and promotes collective motility of carcinoma
AU - Tripodo, Claudio
AU - Sigismund, Sara
AU - Giavazzi, Fabio
AU - Garre, Massimiliano
AU - Corallino, Salvatore
AU - Li, Qingsen
AU - Cavalcanti-Adam, Elisabetta A.
AU - Ascione, Flora
AU - Frittoli, Emanuela
AU - Barbieri, Elisa
AU - Martini, Emanuele
AU - Malinverno, Chiara
AU - Tripodo, Claudio
AU - Beznoussenko, Galina V.
AU - Palamidessi, Andrea
AU - Cerbino, Roberto
AU - Scita, Giorgio
AU - Di Fiore, Pier Paolo
AU - Parazzoli, Dario
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
UR - http://hdl.handle.net/10447/401654
UR - http://www.nature.com/nmat/
M3 - Article
VL - 18
SP - 1252
EP - 1263
JO - Nature Materials
JF - Nature Materials
SN - 1476-1122
ER -