Cited by 1,589Cellular Mechanics and InteractionsProtein Kinase Regulation and GTPase SignalingCancer Cells and Metastasis

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Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells

Gaggioli, Cedric, Hooper, Steven, Hidalgo-Carcedo, Cristina, Grosse, Robert, Marshall, John F., Harrington, Kevin, Sahai, Erik·2007·Nature Cell Biology

DOI 10.1038/ncb1658

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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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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: Hooper, Steven
Hidalgo-Carcedo, Cristina
Grosse, Robert
Marshall, John F.
Harrington, Kevin
Sahai, Erik
Venue: Nature Cell Biology
Publisher: Springer Science and Business Media LLC
Published: 2007-11-25
Volume: 9
Issue: 12
Pages: 1392-1400
ISSN: 1465-7392 (ISSN-L)
1476-4679
DOI: 10.1038/ncb1658
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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Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells

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