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Solid-to-liquid-like transition during cancer progression - Scita

Solid-to-liquid-like transition during cancer progression

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 remains, however, unclear. We showed that perturbation of the basic endocytic machinery is sufficient to promote a transition from a solid to flocking liquid mode of motion in various normal and tumorigenic epithelial ensembles and to promote the progression of early breast cancer lesions that become locally invasive. Aims fo this project is thus: i) to investigate the molecular determinants enabling key endo-factors to promote this mechano-dynamics switch; ii)  determine the pathophysiological relevance of endo-mediated solid-to-liquid transition using a combination of physical approaches, bioengineered devices, 3D matrix, ex vivo and in vivo model systems; iii)  investigate how the acquired tissue fluidification leads to a drastic transcriptional rewiring of cell fate and the emergence of malignant traits.

For published references :
1. Palamidessi, A.; Malinverno, C.; Frittoli, E.; Corallino, S.; Barbieri, E.; Sigismund, S.; Beznoussenko, G. V.; Martini, E.; Garre, M.; Ferrara, I.; Tripodo, C.; Ascione, F.; Cavalcanti-Adam, E. A.; Li, Q.; Di Fiore, P. P.; Parazzoli, D.; Giavazzi, F.; Cerbino, R.; Scita, G., Unjamming overcomes kinetic and proliferation arrest in terminally differentiated cells and promotes collective motility of carcinoma. Nature materials 2019.
2. Malinverno, C.; Corallino, S.; Giavazzi, F.; Bergert, M.; Li, Q.; Leoni, M.; Disanza, A.; Frittoli, E.; Oldani, A.; Martini, E.; Lendenmann, T.; Deflorian, G.; Beznoussenko, G. V.; Poulikakos, D.; Haur, O. K.; Uroz, M.; Trepat, X.; Parazzoli, D.; Maiuri, P.; Yu, W.; Ferrari, A.; Cerbino, R.; Scita, G., Endocytic reawakening of motility in jammed epithelia. Nature materials 2017, 16 (5), 587-596.
3. Giavazzi, F.; Malinverno, C.; Corallino, S.; Ginelli, F.; Scita, G.; Cerbino, R., Giant fluctuations and structural effects in a flocking epithelium. Journal of Physics D: Applied Physics 2017, 50 (38), 384003.
4. Chepizhko, O.; Giampietro, C.; Mastrapasqua, E.; Nourazar, M.; Ascagni, M.; Sugni, M.; Fascio, U.; Leggio, L.; Malinverno, C.; Scita, G.; Santucci, S.; Alava, M. J.; Zapperi, S.; La Porta, C. A., Bursts of activity in collective cell migration. Proc Natl Acad Sci U S A 2016, 113 (41), 11408-11413.