Aligned forces: origins and mechanisms of cancer dissemination guided by extracellular matrix architecture
Open accessAbstract
Organized extracellular matrix (ECM), in the form of aligned architectures, is a critical mediator of directed cancer cell migration by contact guidance, leading to metastasis in solid tumors. Current models suggest anisotropic force generation through the engagement of key adhesion and cytoskeletal complexes drives contact-guided migration. Likewise, disrupting the balance between cell-cell and cell-ECM forces, driven by ECM engagement for cells at the tumor-stromal interface, initiates and drives local invasion. Furthermore, processes such as traction forces exerted by cancer and stromal cells, spontaneous reorientation of matrix-producing fibroblasts, and direct binding of ECM modifying proteins lead to the emergence of collagen alignment in tumors. Thus, as we obtain a deeper understanding of the origins of ECM alignment and the mechanisms by which it is maintained to direct invasion, we are poised to use the new paradigm of stroma-targeted therapies to disrupt this vital axis of disease progression in solid tumors.
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Cell traction deforms the ECM network from curvy and relaxed to stretched and linearized (anisotropic) architecture, typically aligned parallel or perpendicular to the tumor edge (TACS).
“The resulting cell traction then deforms the network from originally curvy and relaxed towards a stretched and linearized (anisotropic) architecture, which typically aligns in parallel or perpendicular orientation to the tumor edge, which is termed tumorassociated collagen signatures (TACS) (Figure 1) [19].”
From Cancer-on-chip models for metastasis: importance of the tumor microenvironment (2024) · cites this paper as [19]
Stiffened ECM causes increased integrin signaling- and actomyosin contraction-mediated mechanocoupling.
“Stiffened ECM causes increased integrin signaling-and actomyosin contractionmediated mechanocoupling.”
From Cancer-on-chip models for metastasis: importance of the tumor microenvironment (2024) · cites this paper as [19]
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- Authors
- Ray, A., & Provenzano, P. P.
- Affiliations
- University of California, San Francisco (US)
- University of Minnesota (US)
- Corresponding author
- Ray, Arja
- Provenzano, Paolo P.
- Venue
- Current Opinion in Cell Biology
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- Elsevier BV
- Published
- 2021-10
- Volume
- 72
- Pages
- 63-71
- ISSN
- 0955-0674 (ISSN-L)
- PMC
- PMC8530881
- OpenAlex
- W3176488157
- Cited by
- 80
- References
- 74
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- 2026: 12 · 2025: 21 · 2024: 14 · 2023: 22 · 2022: 6 · 2021: 4
- FWCI
- 1.45
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- en
- Open access
- bronze
- doi.org
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- Funders
- Cancer Research Institute (CRI2940)
- National Institutes of Health (R01CA245550, U54CA210190)
- American Cancer Society
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Keywords
- extracellular matrix alignment, tumor cell migration, contact guidance, metastasis, tumor invasion, cell adhesion, cytoskeleton, collagen fiber alignment, stroma-targeted therapy, solid tumors
- MeSH terms
- Cell Communication, Cell Movement, Collagen, Extracellular Matrix, Neoplasms, Cell Line, Tumor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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