Time and place:
Tuesday, 30th of April at 14:30-15:30
Auditorium, K building, at the Institute for Cancer Research, Montebello
Meet the speaker - Light refreshments will be served after the talk at the canteen.
Talk title:
Endocytic Tissue fluidification in pathophysiology
Abstract:
The process in which locally confined epithelial malignancies progressively evolve to become invasive cancer cells is associated with the acquisition of cell motility, fostered by a mechanical shift from a solid-like to a liquid-like state, known as unjamming. The biomolecular machinery behind unjamming has only begun to be unraveled, while whether the perturbations associated with this tissue-level mechanical transition impact on phenotypes during carcinoma progression remains unclear. Using a combination of physical approaches, ex vivo and in vivo model systems, we will address these issues and discuss whether an endocytic-driven transition between “solid” and “liquid” states of cell collectives is a complementary gateway to cell migration in pathology, focusing specifically on the progression of early breast cancer lesions that become locally invasive. We will show how these dynamics changes featuring the coexistence of long-range coordinated motion and local cell re-arrangement are sufficient to promote matrix remodeling, and local invasion and exert mechanical stress on individual cell nuclei. This is accompanied by profound transcriptional rewiring, with the unexpected activation of an inflammatory response, change in cell state, and the emergence of malignant traits.
Recent publications:
Frittoli E, Palamidessi A, Iannelli F, Zanardi F, Villa S, Barzaghi L, Abdo H, Cancila V, Beznoussenko GV, Della Chiara G, Pagani M, Malinverno C, Bhattacharya D, Pisati F, Yu W, Galimberti V, Bonizzi G, Martini E, Mironov AA, Gioia U, Ascione F, Li Q, Havas K, Magni S, Lavagnino Z, Pennacchio FA, Maiuri P, Caponi S, Mattarelli M, Martino S, d'Adda di Fagagna F, Rossi C, Lucioni M, Tancredi R, Pedrazzoli P, Vecchione A, Petrini C, Ferrari F, Lanzuolo C, Bertalot G, Nader G, Foiani M, Piel M, Cerbino R, Giavazzi F, Tripodo C, Scita G.
Tissue fluidification promotes a cGAS-STING cytosolic DNA response in invasive breast cancer.
Nat Mater. 2022 Dec 29. doi: 10.1038/s41563-022-01431-x. Online ahead of print.PMID: 36581770
Nader GPF, Agüera-Gonzalez S, Routet F, Gratia M, Maurin M, Cancila V, Cadart C, Palamidessi A, Ramos RN, San Roman M, Gentili M, Yamada A, Williart A, Lodillinsky C, Lagoutte E, Villard C, Viovy JL, Tripodo C, Galon J, Scita G*, Manel N*, Chavrier P*, Piel M*.
Compromised nuclear envelope integrity drives TREX1-dependent DNA damage and tumor cell invasion.
Cell. 2021 Sep 30;184(20):5230-5246.e22
* Equal Contribution
Palamidessi, A., 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, and G. Scita. 2019.
Unjamming overcomes kinetic and proliferation arrest in terminally differentiated cells and promotes collective motility of carcinoma.
Nature Materials. 2019 Jul 22. doi: 10.1038/s41563-019-0425-1