{"about":{"site":"https://codewithpapers.app","non_affiliation":"Code with Papers and Syntology are not affiliated with, endorsed by, or sponsored by Papers with Code, Meta, or the pwc-archive mirror.","licence":"CC BY-SA 4.0","licence_url":"https://creativecommons.org/licenses/by-sa/4.0/legalcode","attribution":"https://codewithpapers.app/attribution","modified":"archive material modified by Syntology; see the attribution page"},"url":"/paper/the-ecm-and-tissue-architecture-are-major","title":"The ECM and tissue architecture are major determinants of early invasion mediated by E-cadherin dysfunction","arxiv_id":null,"date":"2023-08-11","proceeding":"Communications Biology 2023 8","authors":["Soraia Melo","Pilar Guerrero","Maurício Moreira Soares","José Rafael Bordin","Fátima Carneiro","Patrícia Carneiro","Maria Beatriz Dias","João Carvalho","Joana Figueiredo","Raquel Seruca","Rui D. M. Travasso"],"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.","url_abs":"https://www.nature.com/articles/s42003-023-05482-x","url_pdf":"https://www.nature.com/articles/s42003-023-05482-x.pdf","source":{"archive":"pwc-archive (Hugging Face), CC BY-SA 4.0","snapshot":"2025-07-28","licence_url":"https://creativecommons.org/licenses/by-sa/4.0/legalcode","row_kind":"abstracts"},"code_links":[{"paper_slug":"the-ecm-and-tissue-architecture-are-major","repo_url":"https://github.com/Bordin-Lab/espresso-scripts","is_official":1,"mentioned_in_paper":1,"mentioned_in_github":0,"framework":"none","reach":null},{"paper_slug":"the-ecm-and-tissue-architecture-are-major","repo_url":"https://bitbucket.org/Pigueco/vertex_model_python_2.7","is_official":0,"mentioned_in_paper":1,"mentioned_in_github":0,"framework":"none","reach":null},{"paper_slug":"the-ecm-and-tissue-architecture-are-major","repo_url":"https://github.com/phydev/SPiCCAto","is_official":0,"mentioned_in_paper":1,"mentioned_in_github":0,"framework":"none","reach":null}],"tasks":[],"methods":[],"datasets_introduced":[],"methods_introduced":[],"results":[],"syntology":{"syntology_url":null,"atlas_url":null,"mcp":null,"developers":"https://syntology.ai/developers"},"arxiv_metadata":null,"syntology_extracted_results":null}