Matrix mechano-sensing at the invasive front induces a cytoskeletal and transcriptional memory supporting metastasis
Abstract The extracellular matrix (ECM) controls tumour dissemination. We characterise ECM organization in human and mouse tumours, identifying three regions: tumour body, proximal invasive front and distal invasive front. Invasive areas show increased matrix density, fibre thickness, length, and al...
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56299-7 |
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| author | Oscar Maiques Marta C. Sallan Roman Laddach Pahini Pandya Adrian Varela Eva Crosas-Molist Jaume Barcelo Olivia Courbot Yanbo Liu Vittoria Graziani Youssef Arafat Joanne Sewell Irene Rodriguez-Hernandez Bruce Fanshawe Yaiza Jung-Garcia Paul RC Imbert Eloise M. Grasset Jean Albrengues Maria Santacana Anna Macià Jordi Tarragona Xavier Matias-Guiu Rosa M. Marti Sophia Tsoka Cedric Gaggioli Jose L. Orgaz Gilbert O. Fruhwirth Fredrik Wallberg Kai Betteridge Constantino Carlos Reyes-Aldasoro Syed Haider Andrejs Braun Sophia N. Karagiannis Alberto Elosegui-Artola Victoria Sanz-Moreno |
| author_facet | Oscar Maiques Marta C. Sallan Roman Laddach Pahini Pandya Adrian Varela Eva Crosas-Molist Jaume Barcelo Olivia Courbot Yanbo Liu Vittoria Graziani Youssef Arafat Joanne Sewell Irene Rodriguez-Hernandez Bruce Fanshawe Yaiza Jung-Garcia Paul RC Imbert Eloise M. Grasset Jean Albrengues Maria Santacana Anna Macià Jordi Tarragona Xavier Matias-Guiu Rosa M. Marti Sophia Tsoka Cedric Gaggioli Jose L. Orgaz Gilbert O. Fruhwirth Fredrik Wallberg Kai Betteridge Constantino Carlos Reyes-Aldasoro Syed Haider Andrejs Braun Sophia N. Karagiannis Alberto Elosegui-Artola Victoria Sanz-Moreno |
| author_sort | Oscar Maiques |
| collection | DOAJ |
| description | Abstract The extracellular matrix (ECM) controls tumour dissemination. We characterise ECM organization in human and mouse tumours, identifying three regions: tumour body, proximal invasive front and distal invasive front. Invasive areas show increased matrix density, fibre thickness, length, and alignment, with unique radial fibre orientation at the distal invasive front correlating with amoeboid invasive features. Using patient samples and murine models, we find that metastases recapitulate ECM features of the primary tumour. Ex vivo culture of murine cancer cells isolated from the different tumour regions reveals a spatial cytoskeletal and transcriptional memory. Several in vitro models recapitulate the in vivo ECM organisation showing that increased matrix induces 3D confinement supporting Rho-ROCK-Myosin II activity, while radial orientation enhances directional invasion. Spatial transcriptomics identifies a mechano-inflammatory program associated with worse prognosis across multiple tumour types. These findings provide mechanistic insights into how ECM organization shapes local invasion and distant metastasis. |
| format | Article |
| id | doaj-art-442e1924b7c647cf84fc76d1eeba157c |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-442e1924b7c647cf84fc76d1eeba157c2025-08-20T02:12:58ZengNature PortfolioNature Communications2041-17232025-02-0116112310.1038/s41467-025-56299-7Matrix mechano-sensing at the invasive front induces a cytoskeletal and transcriptional memory supporting metastasisOscar Maiques0Marta C. Sallan1Roman Laddach2Pahini Pandya3Adrian Varela4Eva Crosas-Molist5Jaume Barcelo6Olivia Courbot7Yanbo Liu8Vittoria Graziani9Youssef Arafat10Joanne Sewell11Irene Rodriguez-Hernandez12Bruce Fanshawe13Yaiza Jung-Garcia14Paul RC Imbert15Eloise M. Grasset16Jean Albrengues17Maria Santacana18Anna Macià19Jordi Tarragona20Xavier Matias-Guiu21Rosa M. Marti22Sophia Tsoka23Cedric Gaggioli24Jose L. Orgaz25Gilbert O. Fruhwirth26Fredrik Wallberg27Kai Betteridge28Constantino Carlos Reyes-Aldasoro29Syed Haider30Andrejs Braun31Sophia N. Karagiannis32Alberto Elosegui-Artola33Victoria Sanz-Moreno34Cytoskeleton and metastasis Team, The Breast Cancer Now Toby Robins Research Centre Division of Breast Cancer Research, The Institute of Cancer Research, Chester Beatty LaboratoriesCytoskeleton and metastasis Team, The Breast Cancer Now Toby Robins Research Centre Division of Breast Cancer Research, The Institute of Cancer Research, Chester Beatty LaboratoriesSt. John’s Institute of Dermatology, School of Basic and Medical Biosciences, King’s College LondonRandall Division of Cell and Molecular Biophysics, King’s College London, New Hunt’s House, Guy’s CampusCytoskeleton and metastasis Team, The Breast Cancer Now Toby Robins Research Centre Division of Breast Cancer Research, The Institute of Cancer Research, Chester Beatty LaboratoriesCytoskeleton and metastasis Team, The Breast Cancer Now Toby Robins Research Centre Division of Breast Cancer Research, The Institute of Cancer Research, Chester Beatty LaboratoriesCytoskeleton and metastasis Team, The Breast Cancer Now Toby Robins Research Centre Division of Breast Cancer Research, The Institute of Cancer Research, Chester Beatty LaboratoriesCell and Tissue Mechanobiology Laboratory, The Francis Crick InstituteCytoskeleton and metastasis Team, The Breast Cancer Now Toby Robins Research Centre Division of Breast Cancer Research, The Institute of Cancer Research, Chester Beatty LaboratoriesCytoskeleton and metastasis Team, The Breast Cancer Now Toby Robins Research Centre Division of Breast Cancer Research, The Institute of Cancer Research, Chester Beatty LaboratoriesDepartment of Computer Science, City St George’s, University of LondonCentre for Tumour Microenvironment, Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse SquareCentre for Tumour Microenvironment, Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse SquareRandall Division of Cell and Molecular Biophysics, King’s College London, New Hunt’s House, Guy’s CampusCytoskeleton and metastasis Team, The Breast Cancer Now Toby Robins Research Centre Division of Breast Cancer Research, The Institute of Cancer Research, Chester Beatty LaboratoriesCMR Advanced Bio-imaging Facility, Centre for Microvascular Research, Queen Mary University of London, John Vane Science Building, Charterhouse SquareUniversity Cote d’Azur, CNRS UMR7284, INSERM U1081, Institute for Research on Cancer and Aging, Nice (IRCAN)University Cote d’Azur, CNRS UMR7284, INSERM U1081, Institute for Research on Cancer and Aging, Nice (IRCAN)Department of Pathology and Molecular Genetics, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLleida, CIBERONCOncologic Pathology Group, IRBLleida, Departments of Experimental Medicine and Basic Medical Sciences, University of LleidaDepartment of Pathology and Molecular Genetics, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLleida, CIBERONCDepartment of Pathology and Molecular Genetics, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLleida, CIBERONCDepartment of Dermatology, Hospital Universitari Arnau de Vilanova, CIBERONC, University of Lleida, CIBERONC, IRB LleidaDepartment of Informatics, Faculty of Natural and Mathematical Sciences, King’s College London, Bush HouseUniversity Cote d’Azur, CNRS UMR7284, INSERM U1081, Institute for Research on Cancer and Aging, Nice (IRCAN)Centre for Tumour Microenvironment, Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse SquareComprehensive Cancer Centre, School of Cancer and Pharmaceutical Sciences, King’s College LondonQuell Therapeutics, Translation & Innovation Hub, 84 Wood LnLight Microscopy Facility, The Institute of Cancer Research, Chester Beatty LaboratoriesDepartment of Computer Science, City St George’s, University of LondonBreast Cancer Research Bioinformatics Group, Chester Beatty LaboratoriesCentre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse SquareSt. John’s Institute of Dermatology, School of Basic and Medical Biosciences, King’s College LondonDepartment of Computer Science, City St George’s, University of LondonCytoskeleton and metastasis Team, The Breast Cancer Now Toby Robins Research Centre Division of Breast Cancer Research, The Institute of Cancer Research, Chester Beatty LaboratoriesAbstract The extracellular matrix (ECM) controls tumour dissemination. We characterise ECM organization in human and mouse tumours, identifying three regions: tumour body, proximal invasive front and distal invasive front. Invasive areas show increased matrix density, fibre thickness, length, and alignment, with unique radial fibre orientation at the distal invasive front correlating with amoeboid invasive features. Using patient samples and murine models, we find that metastases recapitulate ECM features of the primary tumour. Ex vivo culture of murine cancer cells isolated from the different tumour regions reveals a spatial cytoskeletal and transcriptional memory. Several in vitro models recapitulate the in vivo ECM organisation showing that increased matrix induces 3D confinement supporting Rho-ROCK-Myosin II activity, while radial orientation enhances directional invasion. Spatial transcriptomics identifies a mechano-inflammatory program associated with worse prognosis across multiple tumour types. These findings provide mechanistic insights into how ECM organization shapes local invasion and distant metastasis.https://doi.org/10.1038/s41467-025-56299-7 |
| spellingShingle | Oscar Maiques Marta C. Sallan Roman Laddach Pahini Pandya Adrian Varela Eva Crosas-Molist Jaume Barcelo Olivia Courbot Yanbo Liu Vittoria Graziani Youssef Arafat Joanne Sewell Irene Rodriguez-Hernandez Bruce Fanshawe Yaiza Jung-Garcia Paul RC Imbert Eloise M. Grasset Jean Albrengues Maria Santacana Anna Macià Jordi Tarragona Xavier Matias-Guiu Rosa M. Marti Sophia Tsoka Cedric Gaggioli Jose L. Orgaz Gilbert O. Fruhwirth Fredrik Wallberg Kai Betteridge Constantino Carlos Reyes-Aldasoro Syed Haider Andrejs Braun Sophia N. Karagiannis Alberto Elosegui-Artola Victoria Sanz-Moreno Matrix mechano-sensing at the invasive front induces a cytoskeletal and transcriptional memory supporting metastasis Nature Communications |
| title | Matrix mechano-sensing at the invasive front induces a cytoskeletal and transcriptional memory supporting metastasis |
| title_full | Matrix mechano-sensing at the invasive front induces a cytoskeletal and transcriptional memory supporting metastasis |
| title_fullStr | Matrix mechano-sensing at the invasive front induces a cytoskeletal and transcriptional memory supporting metastasis |
| title_full_unstemmed | Matrix mechano-sensing at the invasive front induces a cytoskeletal and transcriptional memory supporting metastasis |
| title_short | Matrix mechano-sensing at the invasive front induces a cytoskeletal and transcriptional memory supporting metastasis |
| title_sort | matrix mechano sensing at the invasive front induces a cytoskeletal and transcriptional memory supporting metastasis |
| url | https://doi.org/10.1038/s41467-025-56299-7 |
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