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Cited by 248

The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.

Mesenchymal Cancer Cell-Stroma Crosstalk Promotes Niche Activation, Epithelial Reversion, and Metastatic Colonization

Open access
del Pozo Martin, Yaiza, Park, Danielle, Ramachandran, Anassuya, Ombrato, Luigi, Calvo, Fernando, Chakravarty, Probir, Spencer-Dene, Bradley, Derzsi, Stefanie, Hill, Caroline S., Sahai, Erik, Malanchi, Ilaria·2015·Cell Reports

Abstract

During metastatic colonization, tumor cells must establish a favorable microenvironment or niche that will sustain their growth. However, both the temporal and molecular details of this process remain poorly understood. Here, we found that metastatic initiating cells (MICs) exhibit a high capacity for lung fibroblast activation as a result of Thrombospondin 2 (THBS2) expression. Importantly, inhibiting the mesenchymal phenotype of MICs by blocking the epithelial-to-mesenchymal transition (EMT)-associated kinase AXL reduces THBS2 secretion, niche-activating ability, and, consequently, metastatic competence. Subsequently, disseminated metastatic cells revert to an AXL-negative, more epithelial phenotype to proliferate and decrease the phosphorylation levels of TGF-β-dependent SMAD2-3 in favor of BMP/SMAD1-5 signaling. Remarkably, newly activated fibroblasts promote this transition. In summary, our data reveal a crosstalk between cancer cells and their microenvironment whereby the EMT status initially triggers and then is regulated by niche activation during metastatic colonization.

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Registry

Crossref · 10.1016/j.celrep.2015.11.025

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Metadata

Authors
del Pozo Martin, Y., Park, D., Ramachandran, A., Ombrato, L., Calvo, F., Chakravarty, P., Spencer-Dene, B., Derzsi, S., Hill, C. S., Sahai, E., & Malanchi, I.
Venue
Cell Reports
Publisher
Elsevier BV
Published
2015-12
Volume
13
Issue
11
Pages
2456-2469
ISSN
2211-1247 (ISSN-L)
OpenAlex
W2186103292
Cited by
248
References
8
FWCI
10.01
Type
journal article
Language
en
Open access
gold

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