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.

Unjamming overcomes kinetic and proliferation arrest in terminally differentiated cells and promotes collective motility of carcinoma / A. Palamidessi, C. Malinverno, E. Frittoli, S. Corallino, E. Barbieri, S. Sigismund, G.V. Beznoussenko, E. Martini, M. Garre, I. Ferrara, C. Tripodo, F. Ascione, E.A. Cavalcanti-Adam, Q. Li, P.P. Di Fiore, D. Parazzoli, F. Giavazzi, R. Cerbino, G. Scita. - In: NATURE MATERIALS. - ISSN 1476-1122. - 18:11(2019 Nov), pp. 1252-1263.

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

A. Palamidessi
Primo
;
C. Malinverno
Secondo
;
S. Sigismund;P.P. Di Fiore;F. Giavazzi
;
R. Cerbino
Penultimo
;
G. Scita
Ultimo
2019

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.
Settore MED/04 - Patologia Generale
   Light for Life
   L4L
   FONDAZIONE CARIPLO
   2016-0998

   Role of the YAP/TAZ transcriptional regulators in cancer chemoresistance
   MINISTERO DELL'ISTRUZIONE E DEL MERITO
   2017HWTP2K_003
nov-2019
22-lug-2019
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/668340
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