Article abstract

Nature Cell Biology 9, 1392 - 1400 (2007)
Published online: 25 November 2007 | doi:10.1038/ncb1658

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

Cedric Gaggioli1, Steven Hooper1, Cristina Hidalgo-Carcedo1, Robert Grosse2, John F. Marshall3, Kevin Harrington4 & Erik Sahai1

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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  1. Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK.
  2. Institute of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
  3. Tumour Biology Centre, Cancer Research UK Clinical Centre, Queen Mary's College, Barts and the London Medical and Dental School, Charterhouse Square, London EC1M 6BQ, UK.
  4. Institute of Cancer Research, Cancer Research UK Centre for Cell and Molecular Biology, Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK.

Correspondence to: Erik Sahai1 e-mail: Erik.Sahai@cancer.org.uk



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