The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells
Abstract
Imaging of collectively invading cocultures of carcinoma cells and stromal fibroblasts reveals that the leading cell is always a fibroblast and that carcinoma cells move within tracks in the extracellular matrix behind the fibroblast. The generation of these tracks by fibroblasts is sufficient to enable the collective invasion of the squamous cell carcinoma (SCC) cells and requires both protease- and force-mediated matrix remodelling. Force-mediated matrix remodelling depends on integrins alpha3 and alpha5, and Rho-mediated regulation of myosin light chain (MLC) activity in fibroblasts, but these factors are not required in carcinoma cells. Instead, carcinoma cells use Cdc42 and MRCK (myotonic dystrophy kinase-related CDC42-binding protein kinases) mediated regulation of MLC to follow the tracks generated by fibroblasts.
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“These CAFs are characterized by the expression of specific markers, such as desmin and fibroblast activation protein, and are now recognized as key contributors to ECM remodeling, angiogenesis, and metastasis [36,37,38,39,40].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [37]
In the citing paper
“This depends on RHO and RAB GTPase-mediated control of integrin-mediated adhesions and the actomyosin cytoskeleton81–83 and is linked to downregulation of the transmembrane receptor CD36 (also known as platelet glycoprotein 4)84.”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [81]
In the citing paper
“Although chemical crosslinks are not readily reversed, the production of matrix proteases allows the tumour matrix to be remodelled, and this can lead to the generation of permissive tracks that allow cancer cell invasion81.”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [81]
In the citing paper
“In addition, CAFs secrete substantial amounts of growth factors, proinflammatory cytokines, and chemokines, particularly TGF-β, IL-6, and CC-chemokine ligand 2, which recruit immunosuppressive cells into the tumor stroma and lead to immune escape 20-22.”
From TBX3 shapes an immunosuppressive microenvironment and induces immunotherapy resistance (2025) · cites this paper as [22]
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Metadata
- Authors
- Gaggioli, C., Hooper, S., Hidalgo-Carcedo, C., Grosse, R., Marshall, J. F., Harrington, K., & Sahai, E.
- Affiliations
- Cancer Research UK (GB)
- Heidelberg University (DE)
- Queen Mary University of London (GB)
- Institute of Cancer Research (GB)
- Corresponding author
- Sahai, Erik
- ORCID
- Venue
- Nature Cell Biology
- Published
- 2007-11-25
- Volume
- 9
- Issue
- 12
- Pages
- 1392-1400
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W1977381126
- Cited by
- 1,589
- References
- 32
- Citations by year
- 2026: 57 · 2025: 75 · 2024: 70 · 2023: 108 · 2022: 97 · 2021: 110 · 2020: 117 · 2019: 106 · 2018: 93 · 2017: 100 · 2016: 86 · 2015: 87 · 2014: 92 · 2013: 79 · 2012: 80
- FWCI
- 20.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- collective invasion, carcinoma cells, stromal fibroblasts, Rho GTPases, Cdc42, MRCK, myosin light chain, integrin alpha3, integrin alpha5, extracellular matrix remodeling, squamous cell carcinoma, cell tracks
- MeSH terms
- Carcinoma, Squamous Cell, Cell Movement, Cells, Cultured, Extracellular Matrix, Fibroblasts, Heat-Shock Proteins, Humans, Neoplasm Invasiveness, Myosin Light Chains, rho GTP-Binding Proteins, cdc42 GTP-Binding Protein, Integrin alpha3, Integrin alpha5, HSP27 Heat-Shock Proteins
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