Matrix mechano-sensing at the invasive front induces a cytoskeletal and transcriptional memory supporting metastasis.
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Embargo End Date
ICR Authors
Authors
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
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
Document Type
Journal Article
Date
2025-02-14
Date Accepted
2025-01-13
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.
Citation
Nature Communications, 2025, 16 (1), pp. 1394 -
Source Title
Nature Communications
Publisher
NATURE PORTFOLIO
ISSN
2041-1723
eISSN
2041-1723
Collections
Research Team
BCR Data Science