Article abstract

Nature Cell Biology 11, 1287 - 1296 (2009)
Published online: 18 October 2009 | doi:10.1038/ncb1973

Localized and reversible TGFbold beta signalling switches breast cancer cells from cohesive to single cell motility

Silvia Giampieri1, Cerys Manning1, Steven Hooper1, Louise Jones2, Caroline S. Hill3 & Erik Sahai1

Here we use intravital imaging to demonstrate a reversible transition to a motile state as breast cancer cells spread. Imaging primary tumours revealed heterogeneity in cell morphology and motility. Two distinct modes of motility were observed: collective and single-celled. By monitoring the localization of Smad2 and the activity of a TGFbeta-dependent reporter gene during breast cancer cell dissemination, we demonstrate that TGFbeta signalling is transiently and locally activated in motile single cells. TGFbeta1 switches cells from cohesive to single cell motility through a transcriptional program involving Smad4, EGFR, Nedd9, M-RIP, FARP and RhoC. Blockade of TGFbeta signalling prevented cells moving singly in vivo but did not inhibit cells moving collectively. Cells restricted to collective invasion were capable of lymphatic invasion but not blood-borne metastasis. Constitutive TGFbeta signalling promoted single cell motility and intravasation but reduced subsequent growth in the lungs. Thus, transient TGFbeta signalling is essential for blood-borne metastasis.

Top
  1. Tumour Cell Biology Laboratory, CR-UK London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK.
  2. Centre for Tumour Biology, Institute of Cancer, Charterhouse Square, London, EC1M 6BQ, UK.
  3. Developmental Signalling Laboratory, CR-UK London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK.

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



MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.

NEWS AND VIEWS

TGF-β helps cells fly solo

Nature Cell Biology News and Views (01 Nov 2009)

Cancer biology Emissaries set up new sites

Nature News and Views (08 Dec 2005)

See all 3 matches for News And Views

RESEARCH

Cortical sinus probing, S1P 1 -dependent entry and flow-based capture of egressing T cells

Nature Immunology Article (01 Jan 2009)

See all 10 matches for Research

Extra navigation

Subscribe to Nature Cell Biology

Subscribe

See also

Search PubMed for

Open Innovation Challenges

  • Single-cell Analysis Platform

    • Deadline: Dec 02 2009
    • Reward: $5,000 USD

    This Challenge is looking for novel approaches to analyzing changes at a single-cell level. This is...

  • Delayed Burst Release

    • Deadline: Mar 04 2010
    • Reward: $20,000 USD

    A mechanism is desired that will have little or no release until triggered and then substantially re...

naturejobs

More science jobs
Post a job for free