Matrix mechano-sensing at the invasive front induces a cytoskeletal and transcriptional memory supporting metastasis

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

doi:10.1038/s41467-025-56299-7

Matrix mechano-sensing at the invasive front induces a cytoskeletal and transcriptional memory supporting metastasis

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 MaciàJordi 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

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

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.

Original language	English
Article number	1394
Pages (from-to)	1394
Journal	Nature Communications
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/s41467-025-56299-7
Publication status	Published - 14 Feb 2025

Keywords

Animals
Humans
Extracellular Matrix/metabolism
Mice
Cytoskeleton/metabolism
Neoplasm Metastasis
Neoplasm Invasiveness
Cell Line, Tumor
rho-Associated Kinases/metabolism
Gene Expression Regulation, Neoplastic
Neoplasms/genetics
Mechanotransduction, Cellular
Female
Myosin Type II/metabolism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-025-56299-7

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Maiques, O., Sallan, M. C., Laddach, R., Pandya, P., Varela, A., Crosas-Molist, E., Barcelo, J., Courbot, O., Liu, Y., Graziani, V., Arafat, Y., Sewell, J., Rodriguez-Hernandez, I., Fanshawe, B., Jung-Garcia, Y., Imbert, P. R., Grasset, E. M., Albrengues, J., Santacana, M., ... Sanz-Moreno, V. (2025). Matrix mechano-sensing at the invasive front induces a cytoskeletal and transcriptional memory supporting metastasis. Nature Communications, 16(1), 1394. Article 1394. https://doi.org/10.1038/s41467-025-56299-7

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title = "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 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.",

keywords = "Animals, Humans, Extracellular Matrix/metabolism, Mice, Cytoskeleton/metabolism, Neoplasm Metastasis, Neoplasm Invasiveness, Cell Line, Tumor, rho-Associated Kinases/metabolism, Gene Expression Regulation, Neoplastic, Neoplasms/genetics, Mechanotransduction, Cellular, Female, Myosin Type II/metabolism",

author = "Oscar Maiques and Sallan, {Marta C} and Roman Laddach and Pahini Pandya and Adrian Varela and Eva Crosas-Molist and Jaume Barcelo and Olivia Courbot and Yanbo Liu and Vittoria Graziani and Youssef Arafat and Joanne Sewell and Irene Rodriguez-Hernandez and Bruce Fanshawe and Yaiza Jung-Garcia and Imbert, {Paul Rc} and Grasset, {Eloise M} and Jean Albrengues and Maria Santacana and Anna Maci{\`a} and Jordi Tarragona and Xavier Matias-Guiu and Marti, {Rosa M} and Sophia Tsoka and Cedric Gaggioli and Orgaz, {Jose L} and Fruhwirth, {Gilbert O} and Fredrik Wallberg and Kai Betteridge and Reyes-Aldasoro, {Constantino Carlos} and Syed Haider and Andrejs Braun and Karagiannis, {Sophia N} and Alberto Elosegui-Artola and Victoria Sanz-Moreno",

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doi = "10.1038/s41467-025-56299-7",

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Maiques, O, Sallan, MC, Laddach, R , Pandya, P, Varela, A, Crosas-Molist, E, Barcelo, J, Courbot, O, Liu, Y, Graziani, V, Arafat, Y, Sewell, J, Rodriguez-Hernandez, I , Fanshawe, B, Jung-Garcia, Y, Imbert, PR, Grasset, EM, Albrengues, J, Santacana, M, Macià, A, Tarragona, J, Matias-Guiu, X, Marti, RM, Tsoka, S, Gaggioli, C, Orgaz, JL, Fruhwirth, GO, Wallberg, F, Betteridge, K, Reyes-Aldasoro, CC, Haider, S, Braun, A, Karagiannis, SN, Elosegui-Artola, A & Sanz-Moreno, V 2025, 'Matrix mechano-sensing at the invasive front induces a cytoskeletal and transcriptional memory supporting metastasis', Nature Communications, vol. 16, no. 1, 1394, pp. 1394. https://doi.org/10.1038/s41467-025-56299-7

TY - JOUR

T1 - Matrix mechano-sensing at the invasive front induces a cytoskeletal and transcriptional memory supporting metastasis

AU - Maiques, Oscar

AU - Sallan, Marta C

AU - Laddach, Roman

AU - Pandya, Pahini

AU - Varela, Adrian

AU - Crosas-Molist, Eva

AU - Barcelo, Jaume

AU - Courbot, Olivia

AU - Liu, Yanbo

AU - Graziani, Vittoria

AU - Arafat, Youssef

AU - Sewell, Joanne

AU - Rodriguez-Hernandez, Irene

AU - Fanshawe, Bruce

AU - Jung-Garcia, Yaiza

AU - Imbert, Paul Rc

AU - Grasset, Eloise M

AU - Albrengues, Jean

AU - Santacana, Maria

AU - Macià, Anna

AU - Tarragona, Jordi

AU - Matias-Guiu, Xavier

AU - Marti, Rosa M

AU - Tsoka, Sophia

AU - Gaggioli, Cedric

AU - Orgaz, Jose L

AU - Fruhwirth, Gilbert O

AU - Wallberg, Fredrik

AU - Betteridge, Kai

AU - Reyes-Aldasoro, Constantino Carlos

AU - Haider, Syed

AU - Braun, Andrejs

AU - Karagiannis, Sophia N

AU - Elosegui-Artola, Alberto

AU - Sanz-Moreno, Victoria

PY - 2025/2/14

Y1 - 2025/2/14

N2 - 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.

AB - 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.

KW - Animals

KW - Humans

KW - Extracellular Matrix/metabolism

KW - Mice

KW - Cytoskeleton/metabolism

KW - Neoplasm Metastasis

KW - Neoplasm Invasiveness

KW - Cell Line, Tumor

KW - rho-Associated Kinases/metabolism

KW - Gene Expression Regulation, Neoplastic

KW - Neoplasms/genetics

KW - Mechanotransduction, Cellular

KW - Female

KW - Myosin Type II/metabolism

UR - http://www.scopus.com/inward/record.url?scp=85218490087&partnerID=8YFLogxK

U2 - 10.1038/s41467-025-56299-7

DO - 10.1038/s41467-025-56299-7

M3 - Article

C2 - 39952917

SN - 2041-1723

VL - 16

SP - 1394

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1394

ER -

Matrix mechano-sensing at the invasive front induces a cytoskeletal and transcriptional memory supporting metastasis

Abstract

Keywords

UN SDGs

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