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Localized and reversible TGFβ signalling switches breast cancer cells from cohesive to single cell motility
Open accessAbstract
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 TGFβ-dependent reporter gene during breast cancer cell dissemination, we demonstrate that TGFβ signalling is transiently and locally activated in motile single cells. TGFβ1 switches cells from cohesive to single cell motility through a transcriptional program involving Smad4, EGFR, Nedd9, M-RIP, FARP and RhoC. Blockade of TGFβ 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 TGFβ signalling promoted single cell motility and intravasation but reduced subsequent growth in the lungs. Thus, transient TGFβ signalling is essential for blood-borne metastasis.
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Cites
Shaner, N. C., Campbell, R. E., Steinbach, P. A., Giepmans, B. N. G., Palmer, A. E., & Tsien, R. Y. (2004) · Nature Biotechnology · doi:10.1038/nbt1037 · Cited by 4,619
Kokkinos, M. I., Wafai, R., Wong, M. K., Newgreen, D. F., Thompson, E. W., & Waltham, M. (2007) · Cells Tissues Organs · doi:10.1159/000101320 · Cited by 394
Cited by
Nieto, M. A., Huang, R. Y.-J., Jackson, R. A., & Thiery, J. P. (2016) · Cell · doi:10.1016/j.cell.2016.06.028 · Cited by 4,492
Tumor Metastasis: Molecular Insights and Evolving Paradigms
Valastyan, S., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.09.024 · Cited by 4,011
Metastatic colonization by circulating tumour cells
Massagué, J., & Obenauf, A. C. (2016) · Nature · doi:10.1038/nature17038 · Cited by 2,062
Cancer Invasion and the Microenvironment: Plasticity and Reciprocity
Friedl, P., & Alexander, S. (2011) · Cell · doi:10.1016/j.cell.2011.11.016 · Cited by 1,940
Labelle, M., Begum, S., & Hynes, R. O. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.09.009 · Cited by 1,833
Metadata
- Authors
- Giampieri, S., Manning, C., Hooper, S., Jones, L., Hill, C. S., & Sahai, E.
- Venue
- Nature Cell Biology
- Published
- 2009-10-18
- Volume
- 11
- Issue
- 11
- Pages
- 1287-1296
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2026759417
- Cited by
- 601
- References
- 2
- FWCI
- 20.52
- Type
- journal article
- Language
- en
- Open access
- green
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- Giampieri, S., Manning, C., Hooper, S., Jones, L., Hill, C. S., & Sahai, E. (2009). Localized and reversible TGFβ signalling switches breast cancer cells from cohesive to single cell motility. Nature Cell Biology. https://doi.org/10.1038/ncb1973
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