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

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