ArticleNature cell biology2009
Localized and reversible TGFbeta signalling switches breast cancer cells from cohesive to single cell motility.
Article in Nature cell biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 341 papers.
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Who cites it
341 citing papers in PubMed, 591 citations in OpenAlex.
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281 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.