Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/111182
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Melo, Soraia | - |
dc.contributor.author | Guerrero, Pilar | - |
dc.contributor.author | Soares, Maurício Moreira | - |
dc.contributor.author | Bordin, José Rafael | - |
dc.contributor.author | Carneiro, Fátima | - |
dc.contributor.author | Carneiro, Patrícia | - |
dc.contributor.author | Dias, Maria Beatriz | - |
dc.contributor.author | Carvalho, João | - |
dc.contributor.author | Figueiredo, Joana | - |
dc.contributor.author | Seruca, Raquel | - |
dc.contributor.author | Travasso, Rui D. M. | - |
dc.date.accessioned | 2024-01-04T09:17:07Z | - |
dc.date.available | 2024-01-04T09:17:07Z | - |
dc.date.issued | 2023-11-08 | - |
dc.identifier.issn | 2399-3642 | - |
dc.identifier.uri | https://hdl.handle.net/10316/111182 | - |
dc.description.abstract | Germline mutations of E-cadherin cause Hereditary Diffuse Gastric Cancer (HDGC), a highly invasive cancer syndrome characterised by the occurrence of diffuse-type gastric carcinoma and lobular breast cancer. In this disease, E-cadherin-defective cells are detected invading the adjacent stroma since very early stages. Although E-cadherin loss is well established as a triggering event, other determinants of the invasive process persist largely unknown. Herein, we develop an experimental strategy that comprises in vitro extrusion assays using E-cadherin mutants associated to HDGC, as well as mathematical models epitomising epithelial dynamics and its interaction with the extracellular matrix (ECM). In vitro, we verify that E-cadherin dysfunctional cells detach from the epithelial monolayer and extrude basally into the ECM. Through phase-field modelling we demonstrate that, aside from loss of cell-cell adhesion, increased ECM attachment further raises basal extrusion efficiency. Importantly, by combining phase-field and vertex model simulations, we show that the cylindrical structure of gastric glands strongly promotes the cell's invasive ability. Moreover, we validate our findings using a dissipative particle dynamics simulation of epithelial extrusion. Overall, we provide the first evidence that cancer cell invasion is the outcome of defective cell-cell linkages, abnormal interplay with the ECM, and a favourable 3D tissue structure. | pt |
dc.language.iso | eng | pt |
dc.publisher | Springer Nature | pt |
dc.relation | This work was funded by FEDER funds through the Operational Programme Competitiveness Factors— COMPETE and by national funds by FCT—Foundation for Science and Technology under the projects UIDB/04564/2020 and UIDP/04564/2020 (M.M.S., J.C., R.T.), EXPL/ MED-ONC/0386/2021 and 2022.02665.PTDC (S.M., F.C., P.C., J.F., R.S.), and by Ministerio de Ciencia, Innovación y Universidades/FEDER (Spain/UE) through grant PID2022-141802NB-I00 (BASIC) (PG). J.F. is funded by the “FCT Scientific Employment Stimulus—Institutional Call” program (CEECINST/00056/2021). We acknowledge the American Association of Patients with Hereditary Gastric Cancer “No Stomach for Cancer” (J.F., R.S.), and the project “P.CCC: Centro Compreensivo de Cancro do Porto” - NORTE-01-0145-FEDER-072678, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). We also acknowledge the support of the ALM i3S Scientific Platform, member of the PPBI (PPBI-POCI-01-0145- FEDER-022122). J.R.B. acknowledges the financial support the Brazilian National Council for Scientific and Technological Development (CNPq, proc. 304958/2022-0) and the Research Support Foundation of the State of Rio Grande do Sul (FAPERGS, TO 21/ 2551-0002024-5). M.M.S. thanks European Union’s Horizon 2020 Research and Innovation program under the Marie Skłodowska-Curie Actions Grant, Agreement no. 80113 (Scientia fellowship). | pt |
dc.rights | openAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt |
dc.title | The ECM and tissue architecture are major determinants of early invasion mediated by E-cadherin dysfunction | pt |
dc.type | article | pt |
degois.publication.firstPage | 1132 | pt |
degois.publication.issue | 1 | pt |
degois.publication.title | Communications Biology | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.1038/s42003-023-05482-x | - |
degois.publication.volume | 6 | pt |
dc.date.embargo | 2023-11-08 | * |
dc.identifier.pmid | 37938268 | - |
uc.date.periodoEmbargo | 0 | pt |
dc.identifier.eissn | 2399-3642 | - |
item.grantfulltext | open | - |
item.cerifentitytype | Publications | - |
item.languageiso639-1 | en | - |
item.openairetype | article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | Com Texto completo | - |
crisitem.author.researchunit | CISUC - Centre for Informatics and Systems of the University of Coimbra | - |
crisitem.author.researchunit | CFisUC – Center for Physics of the University of Coimbra | - |
crisitem.author.parentresearchunit | Faculty of Sciences and Technology | - |
crisitem.author.orcid | 0000-0001-9928-7256 | - |
crisitem.author.orcid | 0000-0001-7429-0619 | - |
crisitem.author.orcid | 0000-0002-3015-7821 | - |
crisitem.author.orcid | 0000-0001-6078-0721 | - |
Appears in Collections: | I&D CISUC - Artigos em Revistas Internacionais I&D CFis - Artigos em Revistas Internacionais |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
The-ECM-and-tissue-architecture-are-major-determinants-of-early-invasion-mediated-by-Ecadherin-dysfunctionCommunications-Biology.pdf | 5.35 MB | Adobe PDF | View/Open |
Page view(s)
45
checked on May 8, 2024
Download(s)
17
checked on May 8, 2024
Google ScholarTM
Check
Altmetric
Altmetric
This item is licensed under a Creative Commons License